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Mahesh Shivanna, Alaina Short, Benjamin Wadas, Ramesh Periasamy, Hemant Khanna; Influence of Loss of Retinitis Pigmentosa 2 (RP2) and Retinitis Pigmentosa GTPase Regulator (RPGR) Genes on Inner Retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5984.
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© ARVO (1962-2015); The Authors (2016-present)
Mutations in RP2 and RPGR genes are associated with >85% of X-linked RP, a severe form of retinal dystrophy that leads to blindness. AAV-mediated delivery of RP2 and RPGR in the respective mouse models showed mitigation of the photoreceptor degeneration. Long-term treatment outcome not only depends upon the availability of conducive photoreceptor structure but also on the functionality of the inner neurons (such as rod and cone bipolar cells) and the stress response of the inner retina. Therefore, the goals of this study were to assess inner retinal response to the loss of Rp2 and Rpgr.
Experiments were performed using ~4 and ~6 months old Rp2null and Rpgrko mice respectively as well as age-matched wild type mice. These ages were selected to mimic early disease stages. The eyes were enucleated and processed for cryosectioning. The rod and cone photoreceptors were labeled with rhodopsin antibody and Peanut Agglutinin Lectin (PNA) respectively. The rod and cone bipolar cells were identified by labeling with PKCα and Goα antibodies, and the astrocytes/Muller glia were stained with Glial fibrillary acidic protein (GFAP) antibody.
Reduced expression and shorter projections of Goα and PKCα-positive cells at the photoreceptor-bipolar cell synapse layer (outer plexiform layer) were observed in the Rp2null mice as compared to the wild type mice. In the Rpgrko mice, there was reduced expression of PKCα at the outer plexiform layer when compared to that of wild type mice. Increased GFAP expression was also detected in both the Rp2null and Rpgrko mice.
Our results show that Rp2 or Rpgr ablation leads to remodeling of the outer plexiform layer through reduced synaptic connections of bipolar cells with the photoreceptors. Increased GFAP expression in the Rp2null and Rpgrko mice represented active gliosis by the Muller glia. This study can serve as a basis for further exploring the inner retinal response to the loss of Rp2 and Rpgr and refine the treatment window.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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