Regulatory mechanisms of retinal ganglion cell death in normal tension glaucoma and potential therapies

Normal tension glaucoma(NTG)is a multifactorial optic neuropathy characterized by normal intraocular pressure,progressive retinal ganglion cell(RGC)death,and glaucomatous visual field loss.Recent studies have described the mechanisms underlying the pathogenesis of NTG.In addition to controlling intraocular pressure,neuroprotection and reduction of RGC degeneration may be beneficial therapies for NTG.In this review,we summarized the main regulatory mechanisms of RGC death in NTG,including autophagy,glutamate neurotoxicity,oxidative stress,neuroinflammation,immunity,and vasoconstriction.Autophagy can be induced by retinal hypoxia and axonal damage.In this process,ischemia can cause mutations of optineurin and activate the nuclear factor-kappa B pathway.Glutamate neurotoxicity is induced by the over-stimulation of N-methyl-D-aspartate membrane receptors by glutamate,which occurs in RGCs and induces progressive glaucomatous optic neuropathy.Oxidative stress also participates in NTG-related glaucomatous optic neuropathy.It impairs the mitochondrial and DNA function of RGCs through the apoptosis signal-regulating kinase-JUN N-terminal kinase pathway.Moreover,it increases inflammation and the immune response of RGCs.Endothelin 1 causes endothelial dysfunction and impairment of ocular blood flow,promoting vasospasm and glaucomatous optic neuropathy,as a result of NTG.In conclusion,we discussed research progress on potential options for the protection of RGCs,including TANK binding kinase 1 inhibitors regulating autophagy,N-methyl-D-aspartate receptor antagonists inhibiting glutamate toxicity,ASK1 inhibitors regulating mitochondrial function,and antioxidants inhibiting oxidative stress.In NTG,RGC death is regulated by a network of mechanisms,while various potential targets protect RGCs.Collectively,these findings provide insight into the pathogenesis of NTG and potential therapeutic strategies.

Induction of Ovulation with Clomiphene Citrate Combined with Bromocriptine in Polycystic Ovary Syndrome Patients with Infertility: A Prospective, Randomized, and Controlled Clinical Trial

Background:To investigate the therapeutic effects of bromocriptine(BCT)combined with clomiphene citrate(CC)in the induction of ovulation in polycystic ovary syndrome(PCOS)patients with infertility.Methods:A prospective,randomized,and controlled clinical trial was performed on 100 PCOS patients with infertility.Patients were randomly divided into two groups(n=50),patients in control group were treated with 50 mg CC from day 3 to day 7 of the menstrual cycle,and those in observation group(CC+BCT)were given 50 mg of CC from day 3 to day 7 of the menstrual cycle along with 2.5 mg of BCT daily for the full cycle.Patients in both groups were treated for one cycle.Blood was extracted from patients on day 3 of the menstrual cycle,the day of human chorionic gonadotrophin(hCG)injection,and day 7 after hCG injection to measure serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),prolactin(PRL),estradiol(E_(2)),total testosterone(T)and progestin(P).Vaginal ultrasound was used to determine the thickness of endometrium and follicle size and count.Results:There was no significant difference in basal hormone levels between two groups.The success rate of ovulation induction in control group and observation group was 72.0%and 75.4%,respectively,no significant difference was found between two groups(P>0.05).The ongoing pregnancy rate(18.4%)in observation group was significantly higher than that in control group(8.0%).On the day of hCG injection,no significant differences in the levels of FSH,E_(2),and P were found between two groups,while LH was lower,and levels of PRL and T were significantly lower in observation group than those in control group(all P=0.00).On day 7 after hCG injection,no significant differences in the levels of E_(2) and P were found between two groups,while PRL level was significantly lower in observation group than that in control group,and the endometrial thickness in observation group(10.20±1.92 mm)was significantly higher than that in control group(9.22±1.88 mm)(P=0.01).Conclusions:Compared with the use of CC alone,BCT combined with CC can increase the success rate of ovulation induction-assisted pregnancy in PCOS patients,decrease the levels of PRL,LH,and T and increase the endometrial thickness in implantation window.Those data suggest that dopamine agonist BCT may reduce the pituitary hormone and androgen levels,reduce endometrial vascular resistance,and increase endometrial blood supply to improve the infertility outcomes of PCOS patients with infertility.