Sex differences in corneal neovascularization in response to superficial corneal cautery in the rat.

Autor: Irani YD; Discipline of Ophthalmology, College of Medicine and Public Health, Flinders University, Adelaide, Australia., Pulford E; Discipline of Anatomical Pathology, College of Medicine and Public Health, Flinders University, Adelaide, Australia., Mortimer L; Discipline of Ophthalmology, College of Medicine and Public Health, Flinders University, Adelaide, Australia.; Discipline of Anatomical Pathology, College of Medicine and Public Health, Flinders University, Adelaide, Australia., Irani S; Freemasons Foundation Centre for Men's Health, Adelaide Medical School, University of Adelaide, Adelaide, Australia.; South Australian Health and Medical Research Institute, Adelaide, Australia., Butler L; Freemasons Foundation Centre for Men's Health, Adelaide Medical School, University of Adelaide, Adelaide, Australia.; South Australian Health and Medical Research Institute, Adelaide, Australia., Klebe S; Discipline of Anatomical Pathology, College of Medicine and Public Health, Flinders University, Adelaide, Australia., Williams KA; Discipline of Ophthalmology, College of Medicine and Public Health, Flinders University, Adelaide, Australia.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2019 Sep 03; Vol. 14 (9), pp. e0221566. Date of Electronic Publication: 2019 Sep 03 (Print Publication: 2019).
DOI: 10.1371/journal.pone.0221566
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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