RESUMEN
Expression of the Endothelin-2 (Edn2) mRNA is greatly increased in the photoreceptors (PRs) of mouse models of inherited PR degeneration (IPD). To examine the role of Edn2 in mutant PR survival, we generated Edn2(-/-) mice carrying homozygous Pde6b(rd1) alleles or the Tg(RHO P347S) transgene. In the Edn2(-/-) background, PR survival increased 110% in Pde6b(rd1/rd1) mice at post-natal (PN) day 15, and 60% in Tg(RHO P347S) mice at PN40. In contrast, PR survival was not increased in retinal explants of Pde6b(rd1/rd1) ; Edn2(-/-) mice. This finding, together with systemic abnormalities in Edn2(-/-) mice, suggested that the increased survival of mutant PRs in the Edn2(-/-) background resulted at least partly from the systemic EDN2 loss of function. To examine directly the role of EDN2 in mutant PRs, we used a scAAV5-Edn2 cDNA vector to restore Edn2 expression in Pde6b(rd1/rd1) ; Edn2(-/-) PRs and observed an 18% increase in PR survival at PN14. Importantly, PR survival was also increased after injection of scAAV5-Edn2 into Pde6b(rd1/rd1) retinas, by 31% at PN15. Together, these findings suggest that increased Edn2 expression is protective to mutant PRs. To begin to elucidate Edn2-mediated mechanisms that contribute to PR survival, we used microarray analysis and identified a cohort of 20 genes with >4-fold increased expression in Tg(RHO P347S) retinas, including Fgf2. Notably, increased expression of the FGF2 protein in Tg(RHO P347S) PRs was ablated in Tg(RHO P347S); Edn2(-/-) retinas. Our findings indicate that the increased expression of PR Edn2 increases PR survival, and suggest that the Edn2-dependent increase in PR expression of FGF2 may contribute to the augmented survival.
Asunto(s)
Endotelina-2/metabolismo , Mutación , Células Fotorreceptoras de Vertebrados/metabolismo , Células Fotorreceptoras de Vertebrados/patología , Enfermedades de la Retina/genética , Enfermedades de la Retina/metabolismo , Animales , Hipoxia de la Célula/genética , Supervivencia Celular/genética , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 6/metabolismo , Endotelina-2/genética , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Humanos , Ratones , Ratones Transgénicos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Retina/metabolismo , Retina/patología , Enfermedades de la Retina/patología , Rodopsina/genética , Transducción de Señal/genética , Regulación hacia Arriba/genéticaRESUMEN
Multidisciplinary mental health rehabilitation settings often encounter patients with complex comorbid medical and psychiatric issues that require integrative, multifaceted treatment strategies. Although medication and psychotherapy are typical treatment mainstays, a broader variety of therapeutic options are available, including animal-assisted therapy. Here we describe a patient who received animal-assisted therapy as a psychiatric rehabilitation tool to ameliorate his atypical depression following an assault and subsequent head injury. A review of the relevant literature highlights the therapeutic potential of animal-assisted therapy to restore and maintain patient independence and level of functioning, both of which are key treatment goals.
Asunto(s)
Animales Domésticos/psicología , Trastorno Bipolar/complicaciones , Traumatismos Craneocerebrales/complicaciones , Perros/psicología , Trastornos por Estrés Postraumático/rehabilitación , Violencia/psicología , Adulto , Animales , Antidepresivos/uso terapéutico , Terapia Combinada , Vínculo Humano-Animal , Humanos , Masculino , Rol de la Enfermera , Enfermería Psiquiátrica , Trastornos por Estrés Postraumático/complicaciones , Trastornos por Estrés Postraumático/psicología , Resultado del TratamientoRESUMEN
More than 80 genes associated with human photoreceptor degenerations have been identified. Attention must now turn toward defining the mechanisms that lead to photoreceptor death, which occurs years to decades after the birth of the cells. Consequently, this review focuses on topics that offer insights into such mechanisms, including the one-hit or constant risk model of photoreceptor death; topological patterns of photoreceptor degeneration; mutations in ubiquitously expressed splicing factor genes associated only with photoreceptor degeneration; disorders of the retinal pigment epithelium; modifier genes; and global gene expression analysis of the retina, which will greatly increase our understanding of the downstream events that occur in response to a mutation.