Amelioration of Retinal Degeneration in C3H/HeJ Mice by Intravitreal Injection of Noggin

Date of Award

8-2023

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Arturo Bravo Nuevo

Second Advisor

Mindy George-Weinstein

Third Advisor

Ivan Fernandez-Bueno

Abstract

Retinitis Pigmentosa (RP) is a group of congenital disorders that causes progressive degeneration of the retina and affects every 1/4000 individuals. A sustainable treatment for RP is yet to be determined. Previous studies have shown that Myo/Nog cells, which express skeletal muscle transcription factor MyoD, brain angiogenesis inhibitor BAI1, and bone morphogenetic protein inhibitor Noggin, are neuroprotective to injury in the brain and retina. The mechanism whereby Myo/Nog cells protect neurons is yet to be determined. Previous studies have also shown that Noggin is neuroprotective against neuronal damage and injury. We hypothesize that a single intravitreal injection of Noggin will decrease cell death, slow down retinal thinning, downregulate Myo/Nog cells and BMP signaling, and dampen GFAP induced stress in a murine model of RP using C3H/HeJ mice. In addition, we hypothesize that Noggin treated retinas will experience an improvement in retinal function as measured by the electroretinogram (ERG). To perform this study we used C3H mice homozygous for the PDEGB mutation that causes retinal degeneration. C3H mice were given an intravitreal injection of Noggin at 2.5 weeks of age and control mice received injections of mouse serum albumin (MSA) or phosphate-buffered saline (PBS). Enucleated eyes were fixed, cryosectioned, with labeled with Myo/Nog specific BAI1 monoclonal antibody, TUNEL to detect cell death, SMAD4 to detect BMP signaling, and GFAP to detect glial cell proliferation in the retina, and DAPI for nuclei. ERGs were performed at weeks 3 and 5. Immunofluorescent cell counts and retinal thickness were measured using Nikon Eclipse 80i scope, Nikon DSRi2 camera, and Nikon NIS elements AR program. Results displayed that Noggin was neuroprotective against retinal degeneration in a mouse model of RP by reducing cell death, increasing retinal thickness, downregulating BMP and GFAP markers of stress in the retina, and improving overall retinal function as measured by the ERG.

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