Melanocortins applied intravitreally delay retinal dystrophy in Royal College of Surgeons rats

Background: α-Melanocyte-stimulating hormone (MSH) is a neurotrophic agent. In Royal College of Surgeons (RCS) rats, the effects of an MSH analog (MA) were investigated on: (1) the preservation of photoreceptors in vivo following MA intravitreal injection; (2) whether MA is a mitogenic factor. Methods: The study comprised five RCS rat groups, two injected with different doses of MA, one injected with PBS, and two non-injected groups. A single injection of MA or PBS was applied intravitreally to RCS rats on postnatal day 20 (20p). Photoreceptor preservation on 40p was studied using light microscopy. Considering the mitogenic effect of MA, it was studied whether cell proliferation was induced by MA in cultured retinal pigment epithelium (RPE) using the thymidine uptake technique. Results: In degenerating untreated RCS retinae the number of photoreceptor rows on 40p was 60-70% lower than on 20p. Retinae treated with higher doses of MA revealed on 40p a localized significant photoreceptor rescue in the retinal hemisphere which had been injected. However, only a small area of photoreceptor preservation was noted in the injected hemisphere in retinae treated with the lower MA dose. MA showed no mitogenic effect in endothelial or RPE cell culture in vitro. Conclusions: This study is the first to demonstrate that: (1) intravitreally injected MA promotes a dose-related localized rescue of photoreceptors in RCS retinae which may be related to the hormone's neurotrophic activity; (2) MA has no mitogenic or angiogenic properties; (3) MA, as a neuroprotective agent, might be considered for future treatment of retinal dystrophy.