Dr. Gemma Marfany (co-founder and scientific board member of DBGen) presented an oral communication in ARVO 2019 (held in Vancouver, 2-6 May) to show the most prominent results of the research that his group at the UB-CIBERER (U-718) and DBGEN are currently undertaking to study inherited retinal dystrophies. This work is focused on improved genetic diagnosis and the generation of animal models and human retinal organoids from patients. The ARVO meeting, organized by the American Association for the Research in vision and ophthalmology, is considered the best congress in the field. In ARVO, more than 12.000 attendants from over the world (ocular surgeons, ophthalmologists, and basic researchers specialized in retinal genetics and neuroscience) meet and debate on the latest results in vision science, ocular pathologies, and visual disorders, with several sessions focusing on inherited retinal dystrophies.
In ARVO 2019, the researchers that developed Luxturna, the first commercial gene therapy to treat patients affected with a very early onset of retinal degeneration (Leber congenital amaurosis) caused by biallelic mutations in the RPE65 gene. Concerning new treatments, several groups presented very promising phase I/II gene therapy results for the treatment of X linked retinitis pigmentosa, choroideremia, and retinoschisis as well as a safety/efficacy assessment of cell therapy for dystrophies caused by alteration of the retinal pigment epithelium (RPE). Besides, several sessions and posters showed the progress in novel approaches, such as the use o antisense oligonucleotides or CRISPR-based gene editing for gene therapy and the generation of “personalized” disease models by using hIPSCs (human induced pluripotent stem cells) from patients. Concerning genetic diagnosis, many groups are currently addressing the question of the missing heritability that will explain the unsolved cases in mendelian ocular disorders. These missing mutations are most probably “hidden” variants in the non-coding regions, such as non-canonical splice sites, deep-intronic and regulatory sequences. On the other hand, several sessions presented and debated advances in basic genetics research, mainly by implementing big data analyses, from single cell transcriptomics of developing retinas in several organisms including human fetal retinas, to the integrative omics that combine genomics, transcriptomics and methylomics data to provide a polygenic risk score for glaucoma or macular dystrophies.
Overall, visual and ophthalmologic research are burgeoning fields that will soon provide new gene and cell therapies for personalized medicine of affected patients and is generating new approaches for the identification of both, “hidden” non-coding and regulatory mutations for genetic diagnosis of unsolved mendelian disease cases as well as the informative variants for calculating the polygenic risk score for the most prevalent ocular disorders, glaucoma and age-related macular dystrophy.