Effects And Mechanisms Of Androgen Deprivation On The Meibomian Gland Function

Part 1:Clinical study on ocular surface characteristics of patients with prostate cancer by androgen deprivation therapyObjective:To illustrate the change of ocular surface charaterristics of prostate cancer patients received anderogen deprivation and to investigate the different of the ocular surface characteristics between prostate cancer patients received androgen deprivation with or without dry eye symptoms.Methods:A total of 30 male prostate cancer patients who received androgen deprivation therapy(ADT)were selected.All the candidates were scored through the Ocular Surface Disease Index(OSDI).Then they were divided into 9 patients in the symptomatic group(scores>12)and 21 patients in the asymptomatic group(scores≤12)according to the scores.Another 20 healthy males with age matched were selected as the control group.Each candidates were accepted the following inspection and assessment:(1)eyelid margin assessment;(2)tear film break-up time(TBUT);(3)tear meniscus height(TMH);(4)meibomian gland loss score;(5)meibomian gland secretion score;(6)demodex inspection.Results:The TBUT of the ADT group was significantly shorter than that of the control group.The meibomian gland related examine including the eyelid margin assessment,meibomian gland loss score and meibomian gland secretion score of the ADT group were higher,with statistically significant difference(P<0.05).However there was no significant difference in the TMH and demodex inspection between the two groups(P>0.05).The TBUT of the symptomatic ADT group was significantly shorter than that of asymptomatic group(P<0.05),and the meibomian gland loss score and meibomian gland secretion score of the symptomatic ADT group was higher,with statistically significant difference(P<0.05).The demodex inspection of the symptomatic ADT group was also higher than the asymptomatic group(P<0.05).But there was no significant difference between the two groups in the TMH and the eyelid margin assessment(P>0.05).Conclusion:Androgen levels were associated with significant changes in the relative with meibomian gland function.The subjective symptoms such as dryness and foreign body sensation were more obvious in prostate cancer patients by androgen deprivation therapy that may be caused by MGD and demodex infection.It was recommended to pay more attention to the ocular surface of prostate cancer patients treated with androgen deprivation by perform related examinations of TBUT and meibomian gland morphology and function to provide a more comprehensive prevention and treatment protocols in time.Part 2:Investigation of the mice meibomian gland cells change induced by androgen deficiency and its mechanism.Purpose:To explain the effect and mechanism of androgen deprivation on meibomian gland cells and to investigate the feasibility as a meibomian gland dysfunction model.Method:Eighty eyes of 40 male mice were used.In the study group(n=20),the mice that aged 4 weeks were undergoed castration,sham surgery mice were used as control.The lid margin was observed by slit lamp and the meibography was assessed by Stereoscopic Microscopes at 4-week intervals.The eyelid sections were stained with HE,Oil red O,AR,K10,Ki67 and PPARγ antibody at 16 weeks after castration.Result:Slit lamp examination revealed a markedly plugged orifice and telangiectasia in the eyelid of castrated mice compared to sham group.The meibomian gland ducts gradually dilated and acinars reduced in the castrated group over time.Androgen appear to distinct influence the gross morphology of meibomian gland and to exert a demonstrable effect on lipid by Oil red O staining.Androgen receptors existed within mice meibomian gland acinar cells that were weaker expressing in castrated mice than sham mice.Acinis of castrated mice also showed significantly reduced numbers of Ki67 stained nuclei.Androgen deficiency was associated with alterations in K10 that was obviously overexpressed meibomian gland ducts than that of the sham mice.Meibomian glands of sham mice showed cytoplasmic and perinuclear stain with PPARy antibodies.However,Meibomian glands of castrated mice showed weakly PPARy expression.Conclusion:Androgen can significantly influence the gross morphology of meibomian gland.The meibomian gland was an androgen target organ,which the expression level of androgen receptor was distinct decreased after castration.The PPARy receptor signaling may underlie change in cell proliferation,lipid synthesis and gland atrophy during androgen deficiency.The ocular surface features of castrated mice were similar to clinical MGD,which can be used as an ideal MGD model.