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Ayesha Badar, Lauren Scaggs-Brownie, Amir Reza Hajrasouliha; Effect of chemerin-CMKLR1 pathway on retinal neovascularization. Invest. Ophthalmol. Vis. Sci. 2020;61(7):303.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal neovascularization develops during a variety of ocular diseases and can cause visual impairment. The protein chemerin has been shown to be elevated in the serum and vitreous of patients with diabetic retinopathy, correlated with the clinical stage. We have identified chemerin-receptor (CMKLR1) to be upregulated in fibrovascular proliferative membranes of diabetic patients. Chemerin has been shown to induce angiogenesis in human vascular endothelial cells. We aim our study to define the role of the Chemerin-CMKLR1 axis in aberrant angiogenesis in the retina. We hypothesize that the suppression of chemerin-CMKLR1 pathway will suppress neovascularization.
Scratch test assay of HUVEC cells was assessed in the presence of C15 and PHS (chemerin peptide blockers). For tube formation assay, 2500 cells in 100 ml of growth medium containing C15 or PHS (1, 10, 100, and1000pM) were plated onto a 96 well plate precoated with 50 µl of Matrigel basement membrane. Bright-field digital micrographs were taken at 8h to measure in vitro tube formation. All animal experiments were approved by Indiana University School of Medicine and followed guidelines of the Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Ophthalmic and Visual Research. Wild-type female C57BL/6J mice, 4 to 8 weeks old were anesthetized, then treated with 90 ms duration, 200 mW pulses of an ophthalmic argon green laser, wavelength 532 nm, coupled to a slit lamp. Treatment group received intravitreal volume of C15 at 1pM and PHS at 1000pM at the time of laser treatment (dose adjusted based on in vitro study). 14 days after laser treatment, mice underwent optical coherence tomography using a Micron III imager and fluorescein angiography.
C15 and PHS reduced migration in a dose and time dependent manner (P<0.05) on migration assay. Treatment with C15 and PHS impeded angiogenesis, as evidenced by lack of capillary-like tube formation in dose dependent manner on tube formation assay. Mice treated with C15 at 1pM and PHS at 1000pM dosages showed significantly less neovascular membrane after 14 days compared to control mice on OCT (15mm vs 11mm P<0.05). Mice treated with C15 at 1pM and PHS at 1000pM dosages showed no leakage on FA at 14 days, significantly lower than control mice with leakage area of 79.8 µM (P<0.001).
These findings may elicit a new target in the management of retinal neovascularization.
This is a 2020 ARVO Annual Meeting abstract.
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