Life Sciences & Biotechnology
Title : | Evaluation of IOP lowering property and Anti-fibrotic property of Relaxin on TGFβ2-induced Elevated IOP Ex vivo model of glaucoma using Human Organ Cultured Anterior Segment (HOCAS) |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Glaucoma and Ocular Therapeutics |
Principal Investigator : | Dr. Senthilkumari Srinivasan, Aravind Medical Research Foundation, Tamil Nadu |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | ss_kumari@aravind.org |
Details
Executive Summary : | Relaxin is a heterodimeric peptide hormone with known vaso-dilatory and anti-fibrotic activity. This hormone was first identified by Frederick Hisaw in guinea pig model of pregnancy and parturition. Relaxin hormone was found to loosen pelvic ligaments to facilitate parturition by reducing the density of collagen bundles and relaxing the collagen fibers. However, the IOP lowering property of relaxin was not completely understood. Very few reports found that the IOP was lower in pregnant women in their trimester as compared to non-pregnant women or to first or second trimester. Recent study by Hampel et al (2019) found that relaxin 2 fail to lower IOP and dilate retinal vessels in rats after 1or 3h of application. However, the expression of relaxin2, RXFP1 and RXFP2 were expressed at the ocular surface and in tears suggesting the potential effect in wound healing. Very recently the Relaxin receptor Relaxin/Insulin‑LikeFamily Peptide Receptor 1 (RXFP1) in sections of the anterior segment of the eye and found it in inner uveal, corneoscleral and cribriform meshwork and Schlemm’s canal endothelium where as in another study relaxin gene knockout (Rln‑/‑) mice showed higher IOP, thicker corneas, larger endothelial cells, and lower endothelial cell density and it is also found RXFP1 mRNA expression in the retina, cornea, sclera, and choroid, while RXFP2 was only in the cornea. In our previous study in identifying the differentially expressed genes between steroid responsive and non-responsive human cadaveric eyes in perfusion culture, we found that relaxin 1 was significantly down-regulated in steroid responder eyes as compared to non-responder eyes and its expression was evident in 7d group as compared to 16h DEX treated HTM cells . However, the role of relaxin and its non-allelic gene variants in human aqueous outflow facility was not yet studied. Considering the distribution of relaxin and its receptors in human aqueous outflow pathway tissue, it is hypothesized that relaxin may have an active role in the regulation of outflow facility and IOP in human eye. Therefore, in the present study it is proposed to study the IOP lowering property as well as anti-fibrotic property of relaxin (serelaxin, recombinant relaxin) on TGFβ2-induced elevated IOP ex vivo model of glaucoma using human perfusion cultured anterior segment (HOCAS) and also to investigate the mechanism by which relaxin mediates anti-fibrotic activity in fibrosis induced by TGFβ2. |
Co-PI: | Dr. Sharmila Rajendrababu, Aravind Medical Research Foundation, Madurai, Tamil Nadu-625020 |
Total Budget (INR): | 51,26,240 |
Organizations involved