Abstract P102: Ablation of MMP-9 and H 2 S Treatment Mitigates Ocular Hypertension and Retinal Remodeling

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2018-09, Vol.72 (Suppl_1)
• Main Authors: George, Akash K, Singh, Mahavir, Homme, Rubens P, Metreveli, Naira, Tyagi, Suresh C
• Format: Article
• Language: English
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/hyp.72.suppl_1.P102

Abstract only ABLATION OF MMP-9 AND H 2 S TREATMENT MITIGATES OCULAR HYPERTENSION AND RETINAL REMODELINGAkash K George, Mahavir Singh, Rubens P Homme, Naira Metreveli, Suresh C TyagiDepartment of Physiology, University of Louisville, Louisville, KY 40202, USAFVB/NJ mouse is homozygous for retinal degeneration 1 allele of Pde6b rd1 and as a result it is functionally blind because of retinal degeneration. Further, Mmp9 knockout (KO) mouse is bred on FVB background and null mice for Mmp9 show altered repair of injury in skin, cornea, CNS, bone marrow reconstitution and altered inflammatory responses. We employed Mmp9 KO line for studying various aspects of visual physiology and compared them with that of parental strain FVB/NJ along with wild type C57BL/6J (C57). Since our group has previously demonstrated that increased activity of MMP-9 leads to degradation of ECM, we thus hypothesized that MMP-9 plays crucial role in retinal remodeling followed by leakage of plasma contents into ocular compartment thereby compromising retinal architecture and intraocular pressure. To test this hypothesis we subjected Mmp9 KO, FVB and C57 mice individually for monitoring their intraocular pressure (IOP) and also performed biochemical, fluorescence imaging, visually guided behavioral studies and histological analyses on their retinae. IOP as measured by tonometry revealed a significant increase in eye pressure especially in FVB strain in comparison to Mmp9 KO and C57 mice. Retinal blood vessels’ leakage was measured using FITC-BSA angiography. Our earlier study revealed a decrease in MMP-9 activity by hydrogen sulfide (H 2 S). Here, we also treated FVB mice with H 2 S donor and again measured IOP. Results suggested that higher constitutive MMP-9 activity in FVB mice while there was no detectable activity in Mmp9 KO mice. There was more leakage in FVB as compared to Mmp9 KO. FVB treated with H 2 S showed decreased MMP-9 activity and relatively less leakage of their retinal blood vessels. Ocular as well as systemic blood pressures were higher in FVB as compared to other groups. Visually guided tests revealed improved navigation in FVB after treatment with H 2 S. Together the overall results suggest that MMP-9 is associated with altered vision and that treatment with H 2 S could halt vision loss.