Administration of dutasteride in animal models of retinitis pigmentosa

Purpose: Retinitis pigmentosa (RP) describes a large group of hereditary retinopathies. It mainly affects the rods. However, once the rods have degenerated, the cones, also die, leading to complete blindness. Although, the mutations that cause RP have been identified in different genes, the mechanisms that cause the death of photoreceptor cells are still unknown. Gonadal hormones may play a protective role in RP. Our research group has shown that oral administration of progesterone to RP mice significantly conserves the number of photoreceptors. 5α‐reductase inhibitors (such as dutasteride (DUT)) are approved treatments for androgenic alopecia. Modulation or inhibition of 5α‐reductase activity increases the levels of the neuroprotective steroid progesterone and 17β‐estradiol. The purpose of this study was to administer DUT to RP mice. This may be another form of increasing progesterone levels in the retina and therefore, may be neuroprotective. Methods: Animals were treated in accordance with the ARVO statement for the use of animals. rds mice were treated intraperitoneally with DUT and euthanized on day 21. Haematoxylin–eosin, cell death, and rod and cone immunohistochemistry were performed to determine if DUT was able to delay photoreceptor death. Immunohistochemical techniques were used to study changes in retinal microglia (Iba‐1) and macroglial cells. Neuronal nitric oxide synthase (nNOS) was also quantified. Results: DUT increased photoreceptor survival in rds mice. An increase in iba‐1 positive cells was found in rds retinas and DUT normalized the number, migration and the length and number of branches in these cells. DUT decreased GFAP (glial fibrillar acid protein) expression. We have also observed a slightly increase in nNOS expression in rds mice. DUT administration was also able to decrease nNOS expression. Conclusions: DUT may be used to improve cell survival, to ameliorate retinal micro and macroglial activation as well as alterations in nNOS in RP.