Abstract
Purpose :
Retinitis Pigmentosa (RP) is a group of congenital disorders that manifests with progressive retinal dystrophy and affects 1/4000 individuals. Treatments for RP are limited. The Bone Morphogenetic Protein Noggin was shown to be neuroprotective in the central nervous system, as are Myo/Nog cells that release Noggin in the retina and brain. This study examined the effects of Noggin in a murine model of RP.
Methods :
C3H/HeJ mice homozygous for the PDE6B mutation received a 1 µL intravitreal injection of 25 ng of Noggin /uL, or mouse serum albumin (MSA), or phosphate buffered saline (PBS) at 2.5 weeks of age. At weeks 3-6, eyes were frozen and sections labeled with TUNEL reagents to detect cell death, and antibodies to the downstream mediator of BMP signaling SMAD4, and glial fibrillary acidic protein (GFAP), a marker of Muller cell stress, followed by fluorescent secondary antibodies. Electroretinograms (ERGs) were performed at weeks 3 and 5.
Results :
Treatment with Noggin resulted in a significant reduction in cell death and GFAP and SMAD4 labeling compared to controls throughout all timepoints. Noggin also significantly increased retinal thickness. ERGs displayed significantly greater amplitudes in Noggin treated retinas than controls at weeks 3 and 5.
Conclusions :
BMP signaling and glial cell proliferation are elevated during tissue injury and stress in the retina and brain. Intravitreal injection of Noggin in a murine model of RP improved retinal function, slowed the degenerative characteristics of disease, and reduced retinal stress. These results suggest that Noggin may be therapeutic for the treatment of RP.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.