RESUMO

Microcephaly and chorioretinopathy are genetic disorders that are inherited in an autosomal recessive manner. The most frequent ocular manifestation is the presence of lacunar atrophy in the retina and choroid. The diagnosis of this condition can be challenging as several potential causes and related syndromes need to be ruled out. We present two cases of microcephaly and chorioretinopathy in Mexican patients, their clinical characterization, and discuss the differential diagnoses that should be considered. An 8-year-old girl was examined due to a history of decreased vision in both eyes. Fundus examination showed excavated, well-defined, sectorial, bilateral, and symmetrical areas of chorioretinal atrophy. An 18-year-old male had a history of poor vision since childhood. Previous ophthalmological examinations reported bilateral symmetric chorioretinal atrophy with pigment accumulation. Both patients had a prior diagnosis of microcephaly and language delay. Blood tests and a comprehensive systemic evaluation ruled out intrauterine infections. The electroretinogram showed decreased amplitude and increased implicit time in the photopic and scotopic responses. Genetic tests revealed mutations in the TUBGCP4 gene, leading to a diagnosis of microcephaly and chorioretinopathy. As observed in these cases, there was variability in retinal lesions. The presence of chorioretinal lacunae and genetic testing can help to correctly diagnose this disorder.

RESUMO

To study the macroglia and microglia and the immune role in long-time light exposure in rat eyes, we performed glial cell characterization along the time-course of retinal degeneration induced by chronic exposure to low-intensity light. Animals were exposed to light for periods of 2, 4, 6, or 8 days, and the retinal glial response was evaluated by immunohistochemistry, western blot and real-time reverse transcription polymerase chain reaction. Retinal cells presented an increased expression of the macroglia marker GFAP, as well as increased mRNA levels of microglia markers Iba1 and CD68 after 6 days. Also, at this time-point, we found a higher number of Iba1-positive cells in the outer nuclear layer area; moreover, these cells showed the characteristic activated-microglia morphology. The expression levels of immune mediators TNF, IL-6, and chemokines CX3CR1 and CCL2 were also significantly increased after 6 days. All the events of glial activation occurred after 5-6 days of constant light exposure, when the number of photoreceptor cells has already decreased significantly. Herein, we demonstrated that glial and immune activation are secondary to neurodegeneration; in this scenario, our results suggest that photoreceptor death is an early event that occurs independently of glial-derived immune responses.

Assuntos

Interleucina-6 , Neuroglia , Lesões por Radiação , Retina , Degeneração Retiniana , Animais , Quimiocinas/genética , Quimiocinas/metabolismo , Interleucina-6/metabolismo , Luz , Neuroglia/imunologia , RNA Mensageiro/genética , Lesões por Radiação/etiologia , Lesões por Radiação/imunologia , Ratos , Retina/imunologia , Retina/efeitos da radiação , Degeneração Retiniana/etiologia , Degeneração Retiniana/imunologia

RESUMO

Classical phospholipase D (PLD) isoforms, PLD1 and PLD2, catalyze the hydrolysis of phosphatidylcholine (PC) to generate phosphatidic acid (PA) which can be further dephosphorylated to diacylglycerol (DAG). Through the generation of these lipid messengers, the PLD pathway can modulate several cellular events, such as proliferation, membrane trafficking, autophagy and the inflammatory response, among many others. This review summarizes the participation of canonical PLD isoforms in physiological and pathological responses in the eye. Although the role of the PLD pathway in ocular and retinal response to stress has not been fully elucidated, pharmacological inhibition of these signaling enzymes seems to be a promising therapeutic tool to avoid inflammatory processes in the retina, abnormal cellular proliferation on the ocular surface and pathological neovascularization. On the contrary, the modulation of classical PLDs may potentiate corneal healing. In summary, the knowledge of the role of PLD1 and PLD2 in the molecular basis of ocular inflammatory and degenerative diseases opens new avenues for potential therapeutic exploration.

Assuntos

Fosfolipase D , Olho/metabolismo , Ácidos Fosfatídicos/metabolismo , Fosfolipase D/metabolismo , Isoformas de Proteínas/metabolismo , Transdução de Sinais

RESUMO

The aim of this study is to propose a classification system for the spinocerebellar ataxia type 7 retinal degeneration (SCA7-RD). Twenty patients with molecularly confirmed SCA7 underwent slit lamp examination, fundus photography, and optical coherence tomography (Spectralis®). Scale for the Assessment and Rating of Ataxia (SARA) and International Cooperative Ataxia Rating Scale (ICARS) were applied, and age, sex, age at symptom onset, and number of CAG expansions were recorded. After analyzing the ophthalmological findings in each participant, a panel of retinal disease experts created a qualitative classification system for SCA7-RD comprising four stages. We assessed the correlations of retinal degeneration severity with SARA and ICARS scores, number of CAG repeats in ATXN7 allele, and age at symptom onset. We graded retinal degeneration as stage 1 in nine participants, as stage 2 in five, and as stage 3 in six. No differences in age and visual symptoms duration were found between groups. SARA and ICARS scores correlated with the severity of SCA7-RD on the classification system (p = 0.024 and p = 0.014, respectively). After adjusting for disease duration, retinal disease stage association with SARA and ICARS scores remained significant (ANCOVA, p < 0.05). The classification system for SCA7-RD was able to characterize different disease stages representing the landmarks in the cone-rod dystrophy natural history. Neurodegeneration appears to occur in parallel in the cerebellum and in the visual pathway. We conclude that retinal degeneration in SCA7 is a potential biomarker of the neurological phenotype severity.

Assuntos

Degeneração Retiniana/classificação , Degeneração Retiniana/etiologia , Ataxias Espinocerebelares/complicações , Adulto , Idade de Início , Envelhecimento , Ataxina-7/genética , Cerebelo/diagnóstico por imagem , Feminino , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Retina/diagnóstico por imagem , Células Fotorreceptoras Retinianas Cones , Degeneração Retiniana/diagnóstico por imagem , Células Fotorreceptoras Retinianas Bastonetes , Ataxias Espinocerebelares/diagnóstico por imagem , Tomografia de Coerência Óptica , Repetições de Trinucleotídeos , Testes Visuais , Vias Visuais/diagnóstico por imagem , Adulto Jovem

RESUMO

Background Microcephaly and chorioretinopathy (MCCRP) is a rare neuro-ophthalmologic disorder that causes microcephaly and chorioretinopathy. In a recessive inheritance pattern, there are three types: MCCRP1; MCCRP2 and MCCRP3. MCCRP3 results from pathogenic variants in the tubulin-gamma complex-associated protein 4 (TUBGCP4) gene.Materials and Methods This is a case report of a patient with a molecular diagnosis defined by mutations in the TUBGCP4 gene. Segregation analyses were carried out.Results The molecular investigation found two heterozygous variants c.1380 G > A (p.Trp460*) a novel nonsense variant, and c.1746 G > T (p Leu582=) a synonymous variant in TUBGCP4. The clinical phenotype was characterized by microcephaly, microphthalmia, chorioretinopathy, a punched-out retinal appearance, dysmorphic facial features, decreased visual acuity, and learning difficulties. The clinical features were similar to those described previously in children with MCCRP3. The proband also had additional features including centripetal obesity, stretch marks, acanthosis nigricans, scoliosis, and hypercholesterolemia. These other features could be part of a ciliopathy syndrome.Conclusions MCCRP2 caused by pathogenic variants in PLK4 is well established as a ciliopathy disease. The role of TUBGCP4 is not well established in the cilium physiology. MCCRP3 may be part of the ciliopathy spectrum.

Assuntos

Doenças da Coroide/patologia , Microcefalia/patologia , Proteínas Associadas aos Microtúbulos/genética , Mutação , Doenças Retinianas/patologia , Criança , Doenças da Coroide/genética , Feminino , Humanos , Microcefalia/genética , Fenótipo , Doenças Retinianas/genética

RESUMO

Death of retinal photoreceptors is the basis of prevalent blinding diseases. Since steroids might have a therapeutic role in retinal degenerations, we compared the protective effects of dexamethasone and progesterone on photoreceptor death induced by mifepristone and light exposure. Therefore, we studied the effective protection doses for each steroid in the two models. In addition, we analyzed changes in the levels of pro- and antiapoptotic molecules, glucocorticoid receptors α and ß (GRα and GRß), and rhodopsin under conditions of successful protection and photoreceptor survival. Mifepristone and light exposure selectively damaged photoreceptors. In light exposed retinas, photoreceptors mainly disappeared in the dorsotemporal region, while mifepristone produced a uniform damage. Dexamethasone and progesterone, at the same dose of 4 mg/kg/day for 2 days, preserved over 88% photoreceptor nuclei in both models. Assessment of cell death regulators showed that, in control retinas, both steroids activated BCL-XL, a prosurvival molecule, and decreased BID, a proapoptotic regulator. After steroid treatment of damaged retinas, BCL-XL, BCL2 and BAX showed characteristic patterns depending on the use of dexamethasone or progesterone on mifepristone or light exposed retinas. By contrast, BID decreased with any injury-steroid combination. Changes in GRα or GRß levels did not correlate with survival but were consistent with a mechanism of ligand induced downregulation of receptor expression. GRß might be upregulated by progesterone. Both dexamethasone and progesterone increased retinal rhodopsin stores, suggesting a link between photoreceptor protection and transduction pathways. Results show that dexamethasone and progesterone induced comparable but not identical protection responses in each model.

Assuntos

Dexametasona/farmacologia , Glucocorticoides/farmacologia , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Progesterona/farmacologia , Lesões Experimentais por Radiação/prevenção & controle , Degeneração Retiniana/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Western Blotting , Caspase 3 , Sobrevivência Celular/fisiologia , Antagonistas de Hormônios/toxicidade , Imuno-Histoquímica , Luz/efeitos adversos , Masculino , Camundongos Endogâmicos BALB C , Mifepristona/toxicidade , Células Fotorreceptoras de Vertebrados/metabolismo , Células Fotorreceptoras de Vertebrados/efeitos da radiação , Lesões Experimentais por Radiação/etiologia , Lesões Experimentais por Radiação/metabolismo , Receptores de Glucocorticoides/metabolismo , Degeneração Retiniana/etiologia , Degeneração Retiniana/metabolismo , Rodopsina/metabolismo , Proteína bcl-X/metabolismo

RESUMO

The retinal pigment epithelium (RPE) is a monolayer of pigmented cells whose function is essential for the integrity of the retina and for visual function. Retinal diseases that eventually end in vision loss and blindness involve inflammation, oxidative stress (OS), and alterations in the RPE-photoreceptor cellular partnership. This chapter summarizes the role of lipid signaling pathways and lipidic molecules in RPE cells exposed to inflammatory and OS conditions. The modulation of these pathways in the RPE, through either enzyme inhibitors or receptor stimulation or blockage, could open new therapeutic strategies for retinal degenerative diseases.

Assuntos

Lipídeos/fisiologia , Estresse Oxidativo , Degeneração Retiniana/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Transdução de Sinais , Humanos , Epitélio Pigmentado da Retina/citologia

RESUMO

Müller glial cells (MGC) are stem cells in the retina. Although their regenerative capacity is very low in mammals, the use of MGC as stem cells to regenerate photoreceptors (PHRs) during retina degenerations, such as in retinitis pigmentosa, is being intensely studied. Changes affecting PHRs in diseased retinas have been thoroughly investigated; however, whether MGC are also affected is still unclear. We here investigated whether MGC in retinal degeneration 1 (rd1) mouse, an animal model of retinitis pigmentosa, have impaired stem cell properties or structure. rd1 MGC showed an altered morphology, both in culture and in the whole retina. Using mixed neuron-glial cultures obtained from newborn mice retinas, we determined that proliferation was significantly lower in rd1 than in wild type (wt) MGC. Levels of stem cell markers, such as Nestin and Sox2, were also markedly reduced in rd1 MGC compared to wt MGC in neuron-glial cultures and in retina cryosections, even before the onset of PHR degeneration. We then investigated whether neuron-glial crosstalk was involved in these changes. Noteworthy, Nestin expression was restored in rd1 MGC in co-culture with wt neurons. Conversely, Nestin expression decreased in wt MGC in co-culture with rd1 neurons, as occurred in rd1 MGC in rd1 neuron-glial mixed cultures. These results imply that MGC proliferation and stem cell markers are reduced in rd1 retinas and might be restored by their interaction with "healthy" PHRs, suggesting that alterations in rd1 PHRs lead to a disruption in neuron-glial crosstalk affecting the regenerative potential of MGC.

RESUMO

PURPOSE: We observed four individuals in two unrelated but consanguineous families from Portugal and Brazil affected by early-onset retinal degeneration, sensorineural hearing loss, microcephaly, intellectual disability, and skeletal dysplasia with scoliosis and short stature. The phenotype precisely matched that of an individual of Azorean descent published in 1986 by Liberfarb and coworkers. METHODS: Patients underwent specialized clinical examinations (including ophthalmological, audiological, orthopedic, radiological, and developmental assessment). Exome and targeted sequencing was performed on selected individuals. Minigene constructs were assessed by quantitative polymerase chain reaction (qPCR) and Sanger sequencing. RESULTS: Affected individuals shared a 3.36-Mb region of autozygosity on chromosome 22q12.2, including a 10-bp deletion (NM_014338.3:c.904-12_904-3delCTATCACCAC), immediately upstream of the last exon of the PISD (phosphatidylserine decarboxylase) gene. Sequencing of PISD from paraffin-embedded tissue from the 1986 case revealed the identical homozygous variant. In HEK293T cells, this variant led to aberrant splicing of PISD transcripts. CONCLUSION: We have identified the genetic etiology of the Liberfarb syndrome, affecting brain, eye, ear, bone, and connective tissue. Our work documents the migration of a rare Portuguese founder variant to two continents and highlights the link between phospholipid metabolism and bone formation, sensory defects, and cerebral development, while raising the possibility of therapeutic phospholipid replacement.

Assuntos

Carboxiliases/genética , Carboxiliases/metabolismo , Adolescente , Adulto , Brasil , Exoma/genética , Feminino , Genótipo , Células HEK293 , Perda Auditiva Neurossensorial/genética , Humanos , Deficiência Intelectual/genética , Masculino , Microcefalia/genética , Anormalidades Musculoesqueléticas/genética , Osteocondrodisplasias/genética , Linhagem , Fenótipo , Portugal , Degeneração Retiniana/genética , Síndrome , Adulto Jovem

RESUMO

ABSTRACT Purpose: To compare the intravitreal concentrations of cellular mediators involved in neurodegeneration, inflammation, and angiogenesis in patients with proliferative diabetic retinopathy and other vitreoretinal diseases. Methods: A multiplex bead immunoassay was used to measure vitreous levels of pigment epithelium-derived factor, serum amyloid P, C-reactive protein, complement C4, alpha-1 antitrypsin, vascular endothelial growth factor, platelet-derived growth factor-AA, platelet-derived growth factor-BB, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor alpha and beta in patients undergoing 23-gauge vitrectomy for proliferative diabetic retinopathy and other diagnoses (control group). Results: We evaluated 55 patients, of whom 24 had proliferative diabetic retinopathy and 31 had other diagnoses including vitreous hemorrhage, retinal detachment, macular hole, and epiretinal membrane. Patients with proliferative diabetic retinopathy demonstrated increased levels of serum amyloid P (85.49 vs. 31.38 ng/mL); C-reactive protein (59.89 vs. 41.75 ng/mL), vascular endothelial growth factor (2,330.11 vs. 554.25 pg/mL; p<0.001), platelet-derived growth factor A (127.32 vs. 39.11 pg/mL), platelet-derived growth factor B (29.37 vs. 7.12 pg/mL), interleukin-6 (69.37 vs. 33.58 pg/mL), interleukin-8 (175.25 vs. 59.71 pg/mL), and interleukin-10 (3.70 vs. 1.88 pg/mL); all p<0.004 when compared with the control group. Levels of pigment epithelium-derived factor (30.06 vs. 27.48 ng/mL; p=0.295), complement C4 (570.78 vs. 366.24 ng/mL; p=0.069), and alpha-1-antitrypsin (359.27 vs. 522.44 ng/mL; p=0.264) were not significantly different between the groups. Intravitreal levels of tumor necrosis factor-alpha and tumor necrosis factor-beta were undetectable. Serum Amyloid P, C-reactive protein, platelet-derived growth factor A, platelet-derived growth factor B, interleukin-6, and interleukin-8 were correlated positively with vascular endothelial growth factor. Conclusions: Cellular mediators involved in neurodegeneration and inflammation demonstrated increased levels in the vitreous humor of patients with proliferative diabetic retinopathy and may be part of the pathogenesis of diabetic retinopathy.

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RESUMO Objetivo: Comparar as concentrações intravítreas de mediadores celulares envolvidos na neurodegeneração, inflamação e angiogênese em pacientes com retinopatia diabética proliferativa e outras doenças vítreo-retinianas. Métodos: Um ensaio imunomagnético foi utilizado para medir os níveis vítreos do fator derivado do epitélio pigmentar, amilóide P sérico, proteína-C-reativa, complemento C4, e alfa-1-antitripsina, fator de crescimento do endotélio vascular, fator de crescimento derivado das plaquetas AA, fator de crescimento derivado das plaquetas BB, interleucina-6, interleucina-8, interleucina-10, fator de necrose tumoral alfa e beta em pacientes submetidos à vitrectomia 23-gauge para retinopatia diabética proliferativa ou outros diagnósticos (grupo controle). Resultados: Foram avaliados 55 pacientes, dos quais 24 tinham retinopatia diabética proliferativa e 31 tinham outros diagnósticos, incluindo hemorragia vítrea, descolamento de retina, buraco macular e membrana epirretiniana. Pacientes com retinopatia diabética proliferativa demonstraram níveis aumentados de amilóide P sérico (85,49 vs 31,38 ng/mL), proteína-C-reativa (59,89 vs 41,75 ng/mL), fator de crescimento do endotélio vascular (2.330,11 vs 554,25 pg/mL, p<0.001), fator de crescimento derivado das plaquetas-A: (127,32 vs 39,11 pg/mL), fator de crescimento derivado das plaquetas-B (29,37 vs 7,12 pg/mL), interleucina-6 (69,37 vs 33,58 pg/mL), interleucina-8 (175,25 vs 59,71 pg/mL) e interleucina-10 (3,70 vs 1,88 pg/mL), todos com p<0,004 quando comparados ao grupo controle. Níveis de fator derivado do epitélio pigmentar (30,06 vs 27,48 ng/mL; p=0,295), complemento C4 (570,78 vs 366,24 ng/mL; p=0,069), alfa-1 antitripsina (359,27 vs 522,44 ng/mL; p=0,264) não foram significativamente diferente entre os grupos. Níveis intravítreos de fator de necrose tumoral alfa e fator de necrose tumoral beta foram indetectáveis. O amilóide P sérico, a proteína C-reativa, o fator de crescimento derivado das plaquetas A e B, a interleucina-6 e a interleucina-8 correlacionaram-se positivamente com o fator de crescimento do endotélio vascular. Conclusões: Os medidores celulares envolvidos na neurodegeneração e inflamação demonstraram níveis aumentados no humor vítreo de pacientes com retinopatia diabética proliferativa e podem ser parte da patogênese da retinopatia diabética.

Assuntos

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Degeneração Retiniana/patologia , Corpo Vítreo/patologia , Mediadores da Inflamação/análise , Retinopatia Diabética/patologia , Valores de Referência , Vitrectomia , Proteína C-Reativa/análise , Fator de Crescimento Derivado de Plaquetas/análise , Componente Amiloide P Sérico/análise , Serpinas/análise , Estudos Transversais , Interleucinas/análise , Estatísticas não Paramétricas , Fator A de Crescimento do Endotélio Vascular/análise , Retinopatia Diabética/cirurgia , Proteínas do Olho/análise , Fatores de Crescimento Neural/análise

RESUMO

ABSTRACT - This report presents three patients diagnosed with macular dystrophies with variants in PRPH2. Peripherin-2, the protein of this gene, is important in the morphogenesis and stabilization of the photoreceptor outer segment. Peripherin-2 deficiencies cause cellular apoptosis. Moreover, pathogenic variants in PRPH2 are associated with various diseases, such as pattern, butterfly-shaped pattern, central areolar, adult-onset vitelliform macular, and cone-rod dystrophies as well as retinitis pigmentosa, retinitis punctata albescens, Leber congenital amaurosis, fundus flavimaculatus, and Stargardt disease.

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RESUMO - Este relato apresenta três pacientes com diagnóstico de distrofias maculares com mutações no PRPH2. Periferina 2, a proteína deste gene, é importante na morfogênese e estabilização do segmento externo dos fotorreceptores. Deficiências de periferina 2 causam apoptose celular. Além disso, variantes patogênicas no PRPH2 estão relacionadas a diferentes doenças, como distrofia padrão, distrofia padrão em asa de borboleta, distrofia central areolar, distrofia viteliforme do adulto, retinose pigmentar, distrofia de cones e bastonetes, retinite punctata albscens, amaurose congênita de Leber, fundus flavimaculatus e doença de Stargardt.

Assuntos

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Distrofias Retinianas/genética , Distrofias Retinianas/diagnóstico por imagem , Periferinas/genética , Degeneração Macular/genética , Degeneração Macular/diagnóstico por imagem , Mutação , Angiofluoresceinografia/métodos , Tomografia de Coerência Óptica/métodos , Distrofias Retinianas/patologia , Degeneração Macular/patologia

RESUMO

PURPOSE: To investigate the clinical characteristics and genetic basis of inherited retinal degeneration (IRD) in six unrelated pedigrees from Mexico. METHODS: A complete ophthalmic evaluation including measurement of visual acuities, Goldman kinetic or Humphrey dynamic perimetry, Amsler test, fundus photography, and color vision testing was performed. Family history and blood samples were collected from available family members. DNA from members of two pedigrees was examined for known mutations using the APEX ARRP genotyping microarray and one pedigree using the APEX LCA genotyping microarray. The remaining three pedigrees were analyzed using a custom-designed targeted capture array covering the exons of 233 known retinal degeneration genes. Sequencing was performed on Illumina HiSeq. Reads were mapped against hg19, and variants were annotated using GATK and filtered by exomeSuite. Segregation and ethnicity-matched control sample analyses were performed by dideoxy sequencing. RESULTS: Six pedigrees with IRD were analyzed. Nine rare or novel, potentially pathogenic variants segregating with the phenotype were detected in IMPDH1, USH2A, RPE65, ABCA4, and FAM161A genes. Among these, six were known mutations while the remaining three changes in USH2A, RPE65, and FAM161A genes have not been previously reported to be associated with IRD. Analysis of 100 ethnicity-matched controls did not detect the presence of these three novel variants indicating, these are rare variants in the Mexican population. CONCLUSIONS: Screening patients diagnosed with IRD from Mexico identified six known mutations and three rare or novel potentially damaging variants in IMPDH1, USH2A, RPE65, ABCA4, and FAM161A genes that segregated with disease.

Assuntos

Proteínas do Olho/genética , Mutação , Degeneração Retiniana/genética , Transportadores de Cassetes de Ligação de ATP/genética , Adolescente , Adulto , Idoso , Pré-Escolar , Análise Mutacional de DNA , Proteínas da Matriz Extracelular/genética , Feminino , Determinismo Genético , Técnicas de Genotipagem , Humanos , IMP Desidrogenase/genética , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Linhagem , Fenótipo , Degeneração Retiniana/etnologia , Sequenciamento do Exoma , cis-trans-Isomerases/genética

RESUMO

The retina is part of the central nervous system specially adapted to capture light photons and transmit this information to the brain through photosensitive retinal cells involved in visual and non-visual activities. However, excessive light exposure may accelerate genetic retinal diseases or induce photoreceptor cell (PRC) death, finally leading to retinal degeneration (RD). Light pollution (LP) caused by the characteristic use of artificial light in modern day life may accelerate degenerative diseases or promote RD and circadian desynchrony. We have developed a working model to study RD mechanisms in a low light environment using light-emitting diode (LED) sources, at constant or long exposure times under LP conditions. The mechanism of PRC death is still not fully understood. Our main goal is to study the biochemical mechanisms of RD. We have previously demonstrated that constant light (LL) exposure to white LED produces a significant reduction in the outer nuclear layer (ONL) by classical PRC death after 7 days of LL exposure. The PRCs showed TUNEL-positive labeling and a caspase-3-independent mechanism of cell death. Here, we investigate whether constant LED exposure affects the inner-retinal organization and structure, cell survival and the expression of photopigments; in particular we look into whether constant LED exposure causes the death of retinal ganglion cells (RGCs), of intrinsically photosensitive RGCs (ipRGCs), or of other inner-retinal cells. Wistar rats exposed to 200 lx of LED for 2 to 8 days (LL 2 and LL 8) were processed for histological and protein. The results show no differences in the number of nucleus or TUNEL positive RGCs nor inner structural damage in any of LL groups studied, indicating that LL exposure affects ONL but does not produce RGC death. However, the photopigments melanopsin (OPN4) and neuropsin (OPN5) expressed in the inner retina were seen to modify their localization and expression during LL exposure. Our findings suggest that constant light during several days produces retinal remodeling and ONL cell death as well as significant changes in opsin expression in the inner nuclear layer.

RESUMO

ABSTRACT Purpose: We aimed to compare the retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, and the choroid thickness between patients with Behcet disease and healthy subjects by using spectral domain optical coherence tomography (SD-OCT). Methods: Ninety eyes of 45 healthy subjects and 104 eyes of 52 patients with Behcet disease were included in this study. Rheumatoid factor and C-reactive protein levels were measured by blood testing in the patients. Results: The mean thickness of the retinal nerve fiber layer, ganglion cells layer, and inner plexiform layer were significantly lower in patients with Behcet's disease than in the healthy subjects. The mean choroidal thickness was significantly higher in the patients than in the healthy subjects. Conclusions: SD-OCT was a useful and non-invasive tool for the detection of retinal nerve degeneration and choroidal changes in patients with Behcet disease even in the absence of ocular involvement.

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RESUMO Objetivo: Comparar a camada de fibras nervosas da retina, a camada de células ganglionares, a camada plexiforme interna e a espessura coróide entre os pacientes com doença de Behçet e indivíduos saudáveis usando tomografia de coerência óptica (OCT) de domínio espectral (SD). Métodos: Noventa olhos de 45 indivíduos saudáveis e 104 olhos de 52 pacientes com doença de Behcet foram incluídos no estudo. O fator reumatoide e os níveis de proteína C-reativa foram medidos por exames de sangue em pacientes com doença de Behcet. Resultados: As médias de espessura da camada de fibras nervosas da retina, da camada de células ganglionares e da camada plexiforme interna dos pacientes com Doença de Behcet foram significativamente menores do que o grupo controle. As medidas de espessura coróide média dos pacientes com doença de Behcet foram significativamente mais elevadas do que o grupo controle. Conclusões: Tomografia de coerência óptica é uma ferramenta útil e não invasiva para acompanhar a degeneração nervosa retiniana e as alterações coroidais em pacientes com doença de Behcet, mesmo sem envolvimento ocular.

Assuntos

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Síndrome de Behçet/diagnóstico por imagem , Tomografia de Coerência Óptica , Retina/diagnóstico por imagem , Células Ganglionares da Retina/patologia , Fator Reumatoide/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Corioide/diagnóstico por imagem , Macula Lutea/diagnóstico por imagem , Fibras Nervosas/patologia

RESUMO

The identification of pathways necessary for retinal pigment epithelium (RPE) function is fundamental to uncover therapies for blindness. Prolactin (PRL) receptors are expressed in the retina, but nothing is known about the role of PRL in RPE. Using the adult RPE 19 (ARPE-19) human cell line and mouse RPE, we identified the presence of PRL receptors and demonstrated that PRL is necessary for RPE cell survival via anti-apoptotic and antioxidant actions. PRL promotes the antioxidant capacity of ARPE-19 cells by reducing glutathione. It also blocks the hydrogen peroxide-induced increase in deacetylase sirtuin 2 (SIRT2) expression, which inhibits the TRPM2-mediated intracellular Ca(2+) rise associated with reduced survival under oxidant conditions. RPE from PRL receptor-null (prlr(-/-)) mice showed increased levels of oxidative stress, Sirt2 expression and apoptosis, effects that were exacerbated in animals with advancing age. These observations identify PRL as a regulator of RPE homeostasis.

Assuntos

Envelhecimento/fisiologia , Prolactina/metabolismo , Epitélio Pigmentado da Retina/citologia , Sirtuína 2/metabolismo , Canais de Cátion TRPM/metabolismo , Animais , Apoptose/efeitos dos fármacos , Feminino , Glutationa/metabolismo , Humanos , Masculino , Camundongos , Prolactina/genética , Receptores da Prolactina/genética , Receptores da Prolactina/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Sirtuína 2/genética , Canais de Cátion TRPM/genética

RESUMO

PURPOSE: To report a case of a young patient with retinitis pigmentosa (RP), essential iris atrophy, and glaucoma. CASE REPORT: This report presents a case of a 22-year-old female patient with unilateral glaucoma, increased intraocular pressure, increased cup-disc ratio, iris atrophy, peripheral anterior synechiae, and bilateral RP. DISCUSSION: The patient presented glaucoma due to the iridocorneal endothelial syndrome, despite low age. RP is a bilateral disorder that may be associated with angle-closure glaucoma.

RESUMO

ResumenINTRODUCCIÓN: La retinosis pigmentaria es la forma hereditaria y crónica más común de distrofia retiniana. Esta condición se caracteriza inicialmente por la afectación progresiva de los fotorreceptores y, posteriormente, de otras capas de la retina. En la exploración ocular esta situación se traduce como palidez del disco óptico, disminución vascular y depósitos de pigmento en la retina.CASO CLÍNICO: Se presenta el caso de un paciente masculino de 15 años de edad con una historia de 6 meses de evolución caracterizada por ceguera nocturna y disminución de la visión lateral temporal superior en ambos ojos.CONCLUSIONES: Este tipo de padecimiento ocular distrófico, genético y progresivo comienza durante la adolescencia y condiciona una discapacidad visual.

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AbstractBACKGROUND: Retinitis pigmentosa is the most common chronic and inherited condition of retinal dystrophy. The progressive involvement of retinal photoreceptors and other layers characterize this condition. This situation results in optic disc pallor and retinal pigment deposition vascular attenuation.CASE REPORT: We present the case of a 15-year-old male with a history of 6 months evolution characterized by night blindness and bilateral impairment of superior temporal vision.CONCLUSIONS: This type of dystrophy is a genetic and progressive eye condition that begins during adolescence and produces visual impairment.

RESUMO

BACKGROUND: Retinitis pigmentosa is the most common chronic and inherited condition of retinal dystrophy. The progressive involvement of retinal photoreceptors and other layers characterize this condition. This situation results in optic disc pallor and retinal pigment deposition vascular attenuation. CASE REPORT: We present the case of a 15-year-old male with a history of 6 months evolution characterized by night blindness and bilateral impairment of superior temporal vision. CONCLUSIONS: This type of dystrophy is a genetic and progressive eye condition that begins during adolescence and produces visual impairment.

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PURPOSE: To investigate changes in multifocal electroretinography (mfERG) parameters associated with high dose chloroquine therapy for treatment of malaria in the Amazonia region of Brazil. METHODS: Forty-eight subjects who had received chloroquine treatment for single or multiple malaria infections with a cumulative dose ranging from 1,050 to 27,000mg were included. The control group consisted of 37 healthy aged-matched subjects. Data was collected on amplitude and implicit time of the N1, P1 and N2 waves in the central macular hexagon (R1) and in five concentric rings at different retinal eccentricities (R2-R6). RESULTS: No significant difference was observed in any mfERG parameter between chloroquine treated patients and control subjects. A comparison with previous data obtained from patients with rheumatologic disorders in the same region of Brazil who had received larger cumulative doses of chloroquine and had displayed mfERG changes, indicated that retinal toxicity seems to be dependent on cumulative dose. CONCLUSION: Lack of mfERG changes in the current study suggests that intensive high dose chloroquine therapy for treatment of malaria is not associated with retinal toxicity.

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Atrofia progressiva generalizada da retina (APGR) é uma doença frequente nos cães da raça Cocker Spaniel, caracterizada pela perda progressiva da função retiniana externa e desaparecimento dos fotorreceptores. A doença é bilateral, hereditária, autossômica recessiva, sem predisposição sexual e está frequentemente associada à catarata. Segundo estudos moleculares, a degeneração ocorre por mutação de diversos genes. Nos cães da raça Cocker Spaniel Americano, a doença é observada entre três e cinco anos de idade e, no Cocker Spaniel Inglês, entre quatro e oito anos de idade. Os sinais clínicos mais encontrados são: nictalopia, hiperreflexia tapetal e catarata. O diagnóstico baseia-se no histórico clínico, exame oftalmológico e em exames complementares, como eletrorretinograma, testes genéticos e ultrassom ocular. Este artigo teve como objetivo realizar uma revisão de literatura a respeito da atrofia progressiva generalizada da retina (APGR) em cães da raça Cocker Spaniel portadores de catarata.

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Generalized progressive retinal atrophy (GPRA) is a common disease in Cocker Spaniels dogs characterized by progressive loss of retinal function and disappearance of photoreceptors. The disease is bilateral, hereditary, autosomal recessive, has no sexual predisposition and is frequently associated with cataracts. According to molecular studies the degeneration occurs by a mutation in different genes. In American Cocker Spaniels dogs the disease is observed between three and five years of age and in English Cocker Spaniels between four and eight years old. The clinical signs are: nyctalopia, tapetal hyperreflexia and cataracts. The diagnosis is based on clinical history, ophthalmologic examination and complementary exams such as electroretinography, ocular ultrasound and genetic testing. This article aimed to conduct a review of literature on the generalized progressive retinal atrophy (GPRA) in Cocker Spaniel dogs with cataracts.