Noggin as a Neuroprotectant against Inherited Retinal Degeneration

Purpose : Retinitis Pigmentosa (RP) comprises a group of congenital disorderscharacterized by progressive retinal degeneration, affecting approximately every 1/4,000individuals. Despite its prevalence, effective treatments for RP remain limited. Previousstudies have shown that Bone Morphogenetic Protein (BMP) inhibitor Noggin exertsneuroprotective properties in brain and spinal cord injury models. Furthermore, Noggin-producing Myo/Nog cells are neuroprotective in response to acute injury in both the brainand retina. This study aims to evaluate the neuroprotective potential of Noggin inmitigating the degenerative course of RP in a mouse model.Methods : C3H/HeJ (Rd1) mice homozygous for the PDE6B mutation, which causes retinaldegeneration primarily affecting the outer nuclear layer (ONL), were used as theexperimental model. At 2.5 weeks post-birth, mice we assigned to one of three groups andreceived a single 1 uL intravitreal injection of either phosphate-buffered saline (PBS),mouse serum albumin (MSA), or Noggin. Five eyes from five mice per group were analyzedat each time point. Retinal tissues were assessed at weeks 3, 4, 5, and 6 post-birth usingDAPI staining for nuclei, TUNEL for cell death, BAI1 for Myo/Nog cells, and GFAP for glialcell expression. Retinal thickness was measured in micrometers (um), and retinal functionwas evaluated with scotopic electroretinograms (ERGs) recorded at 10,000 uV intensity.Results : A single intravitreal injection of Noggin significantly reduced neuronal cell death(TUNEL+ cells), compared to groups treated with MSA or PBS. Noggin-treated retinasexhibited reduced retinal stress, indicated by lower expression of GFAP and fewerMyo/Nog cells. Structural preservation was evident, with increased retinal thicknessobserved in Noggin-treated eyes relative to controls. Functional improvements wereconfirmed through ERGs, which revealed higher amplitudes in both a- and b-waves in theNoggin-treated group.Conclusions : Noggin reduces glial activation, Myo/Nog cell proliferation, and preservesretinal structure and function in a murine model of RP. Noggin-treated retinas exhibitedreduced neuronal cell death, maintained retinal thickness, and enhanced ERG amplitudes,highlighting its neuroprotective potential. These results suggest that Noggin may serve asa therapeutic candidate for mitigating RP. Further studies are needed to evaluate its long-term efficacy and broader applications.