Ten-year Follow-up of Familial Nanophthalmos in Three Siblings

Purpose: Nanophthalmos is a rare congenital disorder associated with a high incidence of angle-closure glaucoma..We followed the clinical manifestations of three siblings to evaluate their responses to various treatments.Methods:.Three sisters with nanophthalmos were followed from 2000 to 2013..Glaucoma and cataract treatments were performed whenever indicated.Results: The oldest sister had chronic elevation of intraocular pressure(IOP) and underwent laser peripheral iridotomy(LPI)on both eyes,.followed by uneventful phacoemulsification with intraocular lens(IOL) implantation on the left eye and phacotrabeculectomy with IOL implantation on the right eye.The middle sister had acute elevation of IOP and initially underwent phacoemulsification combined with implantation of two IOLs on her left eye and LPI on her right eye. Severe uveal effusion occurred when phacoemulsification was performed on her right eye 6 years later, but ultimately was completely resolved. In both sisters, stable IOP and visual results were achieved after lensectomy. The youngest sister, who had suspected angle-closure, achieved a stable IOP and visual results with prophylactic LPI alone.Conclusion: In nanophthalmic eyes, the severity of the disease may foreshadow the severity of surgical complications and responses to therapy.

PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis

Glaucoma is the leading cause of irreversible blindness worldwide.In the pathogen-esis of glaucoma,activated microglia can lead to retinal ganglion cells(RGCs)apoptosis and death,however,the molecular mechanisms remain largely unknown.We demonstrate that phospholipid scramblase 1(PLSCR1)is a key regulator promoting RGCs apoptosis and their clearance by microglia.As evidenced in retinal progenitor cells and RGCs of the acute ocular hypertension(AOH)mouse model,overexpressed PLSCR1 induced its translocation from the nucleus to the cytoplasm and cytomembrane,as well as elevated phosphatidylserine exposure and reactive oxygen species generation with subsequent RGCs apoptosis and death.These damages were effectively attenuated by PLSCR1 inhibition.In the AOH model,PLSCR1 led to an increase in M1 type microglia activation and retinal neuroinflammation.Upregulation of PLSCR1 resulted in strongly elevated phagocytosis of apoptotic RGCs by activated microglia.Taken together,our study provides important insights linking activated microglia to RGCs death in the glaucoma pathogenesis and other RGC-related neurodegenerative diseases.