Progesterone anti-inflammatory properties in hereditary retinal degeneration

Abstract

The interactions between steroid gonadal hormones and the retina (a part of the visual system and the central nervous system (CNS)) have received limited attention and beneficial effects of these hormones in retinal diseases is controversial. Retinitis pigmentosa (RP) is the most common cause of retinal hereditary blindness and to date no treatment is available. However, results regarding the effects of progesterone on the progression of RP are promising. With the idea of demonstrating if the progesterone retinal protection in RP is related to its possible anti-inflammatory properties, we have administered orally progesterone to rd10 mice, an animal model of RP. We observed that progesterone decreased photoreceptors cell death, reactive gliosis and the increase in microglial cells caused by RP. We also examined the expression of neuronal and inducible nitric oxide synthase (nNOS and iNOS), the enzyme responsible for NO production. The results demonstrated a decrease in nNOS expression only in control mice treated with progesterone. Inflammation has been related with an increase in lipid peroxidation. Noticeably progesterone administration was able to diminish retinal malondialdehyde (MDA, a lipid peroxidation product) concentrations in rd10 mice. Altogether, we can conclude that progesterone could be a good therapeutic option not only in RP but also for other retinal diseases that have been associated with inflammation and lipid peroxidation.

Progesterone, Lipoic Acid, and Sulforaphane as Promising Antioxidants for Retinal Diseases: A Review

“…Our study also highlighted the multiple benefits of progesterone as it was able to (i) reduce the typical gliosis of this degeneration, (ii) decrease the retinal glutamate concentration, and (iii) increase the GSH concentration. Similar results were found when the administration of progesterone was done in the rd10 mouse model [56]. These results are consistent with those found by Guarneri [34], who pointed out that high levels of glutamate (such as those found in the retina of the rd1 and rd10 mice) lead to an inadequate expression in the retina of the steroidogenic enzymes and an alteration in the production of neurosteroids.…”

Nitrosative Stress in Retinal Pathologies: Review

“…Our group has demonstrated a decrease in iNOS and no significant change in nNOS in the retina of rd10 mice, an RP animal model [56]. These results agree with Yang et al, who in 2007 studied the expression of iNOS in the rd2 mice (another RP mice model).…”

Intravitreal administration of adalimumab delays retinal degeneration in rd10 mice

“…Microglial activation and upregulation of GFAP in Müller glial cells, which commonly indicates gliosis, were previously found in rd10 mice. 7,13,43,44 Activated glial cells can release cytokines such as TNFα that could exacerbate and propagate neuroinflammation. In this study, intravitreal ADA0.375 and ADA4.61 did not reduce GFAP upregulation (paired t test) but ameliorated microglial activation ( Figure 7C, D).…”