Alayna Aamodt
Research Mentor: Lev Prasov
Mentor Department: Ophthalmology and Visual Sciences; Human Genetics, Medicine
Author(s): Alayna Aamodt, Michelle Brinkmeier, Lev Prasov
Session: Session 1 (9:00 AM – 9:50 AM)
Presentation Type: Poster 1
Abstract
MYRF and PRSS56 are both genes that operate in a common pathway to regulate eye size and retinal function through the development of the retina and retinal pigment epithelium(RPE), and the loss of either of these genes leads to nanophthalmos in patients. These two genes were investigated in conjunction using mouse models, with an emphasis on their influence on various eye developmental pathways. A conditional Myrf allele (Myrf flox) that is specifically deleted in the RPE using Rxcre and a mutant Prss56 allele were utilized(1,2). In a Rxcre Myrf flox/flox single mutant, loss of pigmentation in the RPE and retinal degeneration is detected, while in a Prss56 single mutant, eye size is reduced, but retinal thickness is increased. Hematoxylin and Eosin staining was conducted on sectioned eyes from mice postnatal day 0 (P0), P21, and 9 months, in Myrf and Prss56 single and double mutants to measure retina width. Using data from single-cell RNA sequencing, the expression of TMEM98 and cone arrestin (CAR) was identified to be upregulated in the double mutants compared to the single mutants. Myrf has been shown to target TMEM98, while Prss56 has been shown to affect CAR expression. To assess the impact of known Myrf targets in the context of Prss56 loss, TMEM98 antibody immunofluorescent staining was conducted on P0 sections. Additionally, to determine the impact of Prss56 loss in the context of Myrf loss, CAR antibody immunofluorescent staining was conducted on P21 sections. It is expected that the double mutants will have a decrease in retinal size and reduced TMEM98 and CAR expression. In contrast to expectations, the results showed a recovery of eye size, TMEM98, and CAR expression in the double mutant. Future studies will elucidate the molecular mechanism that rescues these phenotypes. ¹ Garnai SJ, Brinkmeier ML, et al. Variants in MYRF cause autosomal dominant and syndromic nanophthalmos in humans and retinal degeneration in mice. PLoS Genet. 2019 ² Nair KS, Hmani-Aifa M, et al. Alteration of the serine protease PRSS56 causes angle-closure glaucoma in mice and posterior microphthalamia in humans and mice. Nat Genet. 2011
