Publication Date:
2015-10-10
Description:
Norgestrel’, a synthetic form of the female hormone progesterone has been identified as potential drug candidate for the treatment of the degenerative eye disease Retinitis Pigmentosa (RP). However, to date, no work has looked at the compound's specific cellular target. Therefore, this study aimed to identify the receptor target of Norgestrel and begin to examine its potential mechanism of action in the retina. In this work, we identify and characterise the expression of progesterone receptors present in the C57 wild type and rd10 mouse model of RP. Classical progesterone receptors A and B (PR A/B), progesterone receptor membrane components 1 and 2 (PGRMC1, PGRMC2) and membrane progesterone receptors (mPR) α, β and γ were found to be expressed. All receptors excluding PR A/B were also found in the 661W photoreceptor cell line. PGRMC1 is a key regulator of apoptosis and its expression is upregulated in the degenerating rd10 mouse retina. Activated by Norgestrel through nuclear trafficking, siRNA knock down of PGRMC1 abrogated the protective properties of Norgestrel on damaged photoreceptors. Furthermore, specific inhibition of PGRMC1 by AG205 blocked Norgestrel-induced protection in stressed retinal explants. Therefore, we conclude that PGRMC1 is crucial to the neuroprotective effects of Norgestrel on stressed photoreceptors. This article is protected by copyright. All rights reserved.
Print ISSN:
0022-3042
Electronic ISSN:
1471-4159
Topics:
Medicine
