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Samantha B. Wang, Mu M. Zhang, Kyle M. Hu, Karsten Gronert; Corneal Macrophage Subtype Population Exhibits Sex and Injury Specific Differences. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6401.
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Inflammation is a hallmark of many ocular diseases and can trigger corneal angiogenesis, a debilitating condition that can lead to loss of vision. It is marked by an influx of inflammatory cells (PMNs and macrophages [MØ]) and is well documented as having sex-specific differences. MØ are critical for angiogenesis. The alternatively activated M2 subtype in particular has been reported to be pro-angiogenic in other tissues. However, whether M2 recruitment exhibits sex-specific differences and if this difference contributes to differential heme/lymph angiogenesis in acute and chronic corneal inflammation remains to be determined.
Acute inflammation was induced in age-matched male and female Balb/c mice by re-abrading corneas 7 days post epithelial removal. Chronic inflammation was elicited by placing an 8-0 silk suture in the apex of the cornea. Vessel formation was quantified via immunohistology using CD31 and LYVE-1 as specific heme and lymph markers, respectively. Relative MØ populations were assessed using expression of specific cell markers measured via real-time PCR.
In the model of acute corneal inflammation, which has been previously shown to exhibit sex-specific differences in wound closure, male expression of CD163, a M2 specific marker, was 1.88 fold higher at 5 days post reinjury compared to females while expression of CD11b, a pan-leukocyte marker, showed no difference. Correlating with the higher ratio of M2, heme-angiogenesis was also amplified in males. In contrast, there was no significant difference in expression of CD163 or CD11b in corneas 7 days post suture placement. This was reflected in a lack of sex-specific differential induction of heme-angiogenesis. Interestingly, males exhibited more lymph-angiogenesis (38±15%) than females in the chronic model of inflammation.
These results provide evidence for sex and injury specific differences in the corneal inflammatory response. Specifically, MØ subpopulations, which are regulated by and work in conjunction with intrinsic inflammatory circuits, are affected by sex and extent of injury. Given the prevalence of sex-related diseases and M2’s role in corneal heme-angiogenesis, the fundamental sex-specific differences in this system warrant further investigation. Also of interest are the mechanisms underlying the differential regulation of lymph-angiogenesis in chronic inflammation.
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