RESUMEN
Severe blinding retinal degenerative diseases have been without treatments that could improve vision until recently. Gene therapy has been in clinical trials for certain inherited retinopathies in which photoreceptors are retained despite severe visual loss. Optogenetics is being discussed for retinal diseases in which there is severe visual loss and nearly complete photoreceptor cell death. As a retinal therapy, optogenetics would be the genetic targeting of light-sensing molecules to residual cells in a degenerate retina. Parallel with scientific advances in optogenetics should be the development of detailed criteria for patient candidacy. Here, molecularly defined retinal degenerations are used to exemplify how some diseases or stages of disease would satisfy the criteria. Measurements are made of the thickness of ganglion cell and the nerve fiber layers of the retina. Whereas the clinical category of retinitis pigmentosa has been most often mentioned for treatment by optogenetics, an argument is made for expanding the target diseases to some early-onset disorders diagnosed as Leber congenital amaurosis.
Asunto(s)
Amaurosis Congénita de Leber/genética , Amaurosis Congénita de Leber/terapia , Optogenética/métodos , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/terapia , Adolescente , Adulto , Transferasas Alquil y Aril/genética , Antígenos de Neoplasias/genética , Proteínas de Ciclo Celular , Niño , Proteínas del Citoesqueleto , Proteínas del Ojo/genética , Humanos , Amaurosis Congénita de Leber/diagnóstico , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Mutación , Proteínas de Neoplasias/genética , Proteínas del Tejido Nervioso/genética , Retina/metabolismo , Retina/patología , Retinitis Pigmentosa/diagnóstico , Tomografía de Coherencia Óptica , Adulto JovenRESUMEN
PURPOSE: To define molecular and ophthalmic features of a rare phenotype in autosomal dominant (ad) retinitis pigmentosa (RP). METHODS: A 32-year-old woman (proband) with adRP and the low-frequency damped electroretinographic (ERG) wavelet phenotype and her mother were studied with optical coherence tomography (OCT), chromatic perimetry and ERG. A previously reported adRP patient with this ERG phenotype (Lam et al) was also studied with OCT. Genotype in the two families was determined with DNA sequencing. RESULTS: ERGs from the proband were identical to those reported previously. Chromatic perimetry and ERG stimulus intensity series indicated that there can be severely reduced rod function in addition to substantial cone dysfunction. A heterozygous deletion in peripherin/RDS (Met152del3 atGAA) was present in the patient and the affected mother. There were foveal cystoid changes and pericentral splitting of the inner nuclear layer. ONL thickness and vision tapered with eccentricity, and 'blind' regions without discernible ONL showed a thickened, delaminated inner retina. Similar OCT findings were present in the reported adRP patient with this ERG; the patient was heterozygous for a 4-bp deletion (Leu107del4 ctGAGT) in PRPF31. CONCLUSIONS: The low-frequency damped ERG wavelet phenotype is genetically heterogeneous. Inner retinal structural abnormalities are also present in this rare disease expression.