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Type: Journal article
Title: Sex differences in corneal neovascularization in response to superficial corneal cautery in the rat
Author: Irani, Y.D.
Pulford, E.
Mortimer, L.
Irani, S.
Butler, L.
Klebe, S.
Williams, K.A.
Citation: PLoS ONE, 2019; 14(9):e0221566-1-e0221566-17
Publisher: PLOS
Issue Date: 2019
ISSN: 1932-6203
Statement of
Yazad D. IraniID, Emily Pulford, Lauren Mortimer, Swati Irani, Lisa Butler, Sonja Klebe, Keryn A. Williams
Abstract: Sex-based differences in susceptibility have been reported for a number of neovascular ocular diseases. We quantified corneal neovascularization, induced by superficial silver nitrate cautery, in male and female inbred albino Sprague-Dawley, inbred albino Fischer 344, outbred pigmented Hooded Wistar and inbred pigmented Dark Agouti rats of a range of ages. Corneal neovascular area was quantified on haematoxylin-stained corneal flatmounts by image analysis. Pro-and anti-angiogenic gene expression was measured early in the neovascular response by quantitative real-time polymerase chain reaction. Androgen and estrogen receptor expression was assessed by immunohistochemistry. Male rats from all strains, with or without ocular pigmentation, exhibited significantly greater corneal neovascular area than females: Sprague-Dawley males 43±12% (n = 8), females 25±5% (n = 12), p = 0.001; Fischer 344 males 38±10% (n = 12) females 27±8% (n = 8) p = 0.043; Hooded Wistar males 32±6% (n = 8) females 22±5% (n = 12) p = 0.002; Dark Agouti males 37±11% (n = 9) females 26±7% (n = 9) p = 0.015. Corneal vascular endothelial cells expressed neither androgen nor estrogen receptor. The expression in cornea post-cautery of Cox-2, Vegf-a and Vegf-r2 was significantly higher in males compared with females and Vegf-r1 was significantly lower in the cornea of males compared to females, p<0.001 for each comparison. These data suggest that male corneas are primed for angiogenesis through a signalling nexus involving Cox-2, Vegf-a, and Vegf receptors 1 and 2. Our findings re-enforce that pre-clinical animal models of human diseases should account for sex-based differences in their design and highlight the need for well characterized and reproducible pre-clinical studies that include both male and female animals.
Keywords: Cornea; Animals; Rats, Inbred Strains; Rats, Inbred F344; Rats; Rats, Sprague-Dawley; Rats, Wistar; Corneal Neovascularization; Disease Models, Animal; Disease Susceptibility; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factor A; Receptors, Androgen; Receptors, Estrogen; Species Specificity; Gene Expression; Sex Characteristics; Female; Male; Cyclooxygenase 2
Rights: © 2019 Irani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0030134695
DOI: 10.1371/journal.pone.0221566
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