Stem cell therapy in retinal diseases

Alteration of the outer retina leads to various diseases such as age-related macular degeneration or retinitis pigmentosa characterized by decreased visual acuity and ultimately blindness.Despite intensive research in the field of retinal disorders,there is currently no curative treatment.Several therapeutic approaches such as cell-based replacement and gene therapies are currently in development.In the context of cell-based therapies,different cell sources such as embryonic stem cells,induced pluripotent stem cells,or multipotent stem cells can be used for transplantation.In the vast majority of human clinical trials,retinal pigment epithelial cells and photoreceptors are the cell types considered for replacement cell therapies.In this review,we summarize the progress made in stem cell therapies ranging from the pre-clinical studies to clinical trials for retinal disease.

Delivery strategies for CRISPR/Cas genome editing tool for retinal dystrophies:challenges and opportunities

CRISPR/Cas,an adaptive immune system in bacteria,has been adopted as an efficient and precise tool for site-specific gene editing with potential therapeutic opportunities.It has been explored for a variety of applications,including gene modulation,epigenome editing,diagnosis,mRNA editing,etc.It has found applications in retinal dystrophic conditions including progressive cone and cone-rod dystrophies,congenital stationary night blindness,X-linked juvenile retinoschisis,retinitis pigmentosa,age-related macular degeneration,leber’s congenital amaurosis,etc.Most of the therapies for retinal dystrophic conditions work by regressing symptoms instead of reversing the genemutations.CRISPR/Cas9 through indel could impart beneficial effects in the reversal of gene mutations in dystrophic conditions.Recent research has also consolidated on the approaches of using CRISPR systems for retinal dystrophies but their delivery to the posterior part of the eye is a major concern due to high molecular weight,negative charge,and in vivo stability of CRISPR components.Recently,non-viral vectors have gained interest due to their potential in tissue-specific nucleic acid(miRNA/siRNA/CRISPR)delivery.This review highlights the opportunities of retinal dystrophies management using CRISPR/Cas nanomedicine.

Clinical Characterization and Frequency of Observation of Hereditary Retinal Diseases： Multicentric Study in Panama in 2012-2013

Retinal dystrophies are genetically determined diseases, implying the loss of function of the retina with a wide phenotypic and genotypic variability. There are very few phenotypic, genotypic and epidemiological data on retinal dystrophies in Latin America. The Objective of this study is to describe the epidemioiogical and clinical characteristics of hereditary retinal and choroidal diseases, in retina practices in Panama. A descriptive study, from 2012 to 2013, was performed in the main retina practices in Panama. All detected patients were given a free appointment to gather their phenotypic characteristics and pedigrees. An incidence of five new cases per year, and an accumulated incidence of 5.35 patients per I0,000 was calculated for the public hospitals. A frequency of 2.7 cases per 1,000 patients was observed in the main retina practices, where 69% had rod-cone dystrophies, 14.3% cone-rod dystrophies, 7.1% Stargardt disease, 4.8% Stargardt-like macular dystrophy and two patients presented other dystrophies. Blindness was the main family antecedent （45.2%）. Retinal pigment was present in 59% and strabismus in 21.4% of the patients. Rod-cone and cone-rod dystrophies had similar geographic distribution and the autosomal recessive inheritance pattern was the most frequently observed. This study gives the first phenotypic data of retinal dystrophies in Panama to orient clinicians for a better diagnosis and phenotyping-genotyping correlation for retinal dystrophies in Central America.

The m^(6)A reader YTHDC2 maintains visual function and retinal photoreceptor survival through modulating translation of PPEF2 and PDE6B

Inherited retinal dystrophies (IRDs) are major causes of visual impairment and irreversible blindness worldwide, while the precise molecular and genetic mechanisms are still elusive. N6-methyladenosine (m^(6)A) modification is the most prevalent internal modification in eukaryotic mRNA. YTH domain containing 2 (YTHDC2), an m^(6)A reader protein, has recently been identified as a key player in germline development and human cancer. However, its contribution to retinal function remains unknown. Here, we explore the role of YTHDC2 in the visual function of retinal rod photoreceptors by generating rod-specific Ythdc2 knockout mice. Results show that Ythdc2 deficiency in rods causes diminished scotopic ERG responses and progressive retinal degeneration. Multi-omics analysis further identifies Ppef2 and Pde6b as the potential targets of YTHDC2 in the retina. Specifically, via its YTH domain, YTHDC2 recognizes and binds m^(6)A-modified Ppef2 mRNA at the coding sequence and Pde6b mRNA at the 5′-UTR, resulting in enhanced translation efficiency without affecting mRNA levels. Compromised translation efficiency of Ppef2 and Pde6b after YTHDC2 depletion ultimately leads to decreased protein levels in the retina, impaired retinal function, and progressive rod death. Collectively, our finding highlights the importance of YTHDC2 in visual function and photoreceptor survival, which provides an unreported elucidation of IRD pathogenesis via epitranscriptomics.