Elizabeth Rossin, MD, PhD: Genetic Associations of Epiretinal Membrane

Elizabeth Rossin, MD, PhD

Credit: Massachusetts Eye and Ear

New research presented at the 2023 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting identified six novel loci for non-diabetic epiretinal membrane, a common cause of visual decline in people 60 years and older.

In particularly, the analysis indicates DHX36 may play an important role in the pathophysiology of ERM, given its expression in pathologic tissue specimens, and could be a potential therapeutic target area.

“Now, we have answers as to what genes may be causing epiretinal membrane, and what genes are also expressed to the membranes, and thereby point to specific targets to go after therapeutically,” Elizbeth Rossin, MD, Massachusetts Eye and Ear told HCPLive at ARVO 2023.

Despite its common occurrence in the older population, there is no medical treatment besides surgery, which may not fully restore vision due to permanent neuronal damage from the epiretinal membrane. However, the condition appears to cluster in families and a better understanding of this relationship could help identify novel targets for therapeutic intervention.

The condition is a fibroceullar proliferation on the surface of the retina, occurring in 1-2% of the population, but aside from a few known comorbidities known to be risk factors, the pathophysiology is not well-understood. Additionally, there are currently no known genetic risk factors. Rossin and colleagues aimed to identify genetic risk loci for epiretinal membrane and to use single cell expression data from patient-derived pathologic specimens to highlight critical genes.

The investigative team identified 2,995 cases and 341,547 controls in the FinnGen study based in Finland. A series of filters were applied to cases and controls in order to remove all patients with any form of diabetic retinopathy, which can lead to different forms of epiretinal membrane.The investigative team conducted a genome-wide association study with sex, age at death or end of follow-up, first 10 principal components, genotyping array, and genotyping batch as covariates.

For the loci that achieved genome-wide significance (5 x 10 ^-8), investigators explored which genes were expressed uniformly in 5 patient-derived epiretinal membranes peeled during surgery for proliferative vitreoretinopathy at the investigator’s institution. The team additionally queried expression quantitative trait loci in the Genotype-Tissue Expression (GTEx) project version 8.

Investigators identified 6 novel loci (P < 5 x 10 ^-8) for non-diabetic epiretinal membrane. Upon analysis, in the most significant locus, the lead variant (rs28630834 A>G) is intronic within DHX36 and is associated with increased DHX36 expression in cultured fibroblasts (P < 8.7 x 10 ^-7) in GTEx. The analysis suggested DHX36, and not the other genes in the locus, was highly expressed in all surgical membrane specimens and could play an important role in primary epiretinal membrane pathophysiology.

Rossin and colleagues noted, to their knowledge, their report is one of the earliest on the genetic associations for epiretinal membrane in which they identified 5 associated regions of the genome. For more insight into the analysis on epiretinal membranes, watch our full interview with Rossin from ARVO 2023 below.

Elizabeth Rossin, MD, reports having received consultant fees from Genentech.

References

Rossin E, Ramo JT, Miller WP, Bejjani R, Sobrin L, Vavvas DG, Miller JB, Wang X, Daly M, Eliott Dean, Palotie A, Kim LA. Genome-wide association study of epiretinal membrane in the Finnish population identifies novel associated genes that are expressed in patient-derived pathologic membranes. Presented at the 2023 Association for Research in Vision and Ophthalmology Annual Meeting; April 2023; New Orleans, LA.