These results indicate that STAT3, but not MAPK, can critically regulate photoreceptor development during mouse retina development.

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Miniature postsynaptic currents (mPSCs) were examined on autaptic innervation of single rat retinal ganglion cells in low density cultures. Removal of Ca2+ from bath solution or blocking of Ca2+ channels by Cd2+ had no detectable effect on mPSC frequency or amplitude. Thapsigargin, an agent for mobilization of Ca2+ from internal stores, increased mPSC frequency 3-5-fold in control, Ca2+-free or Cd2+-containing solutions. The inositol 1,4,5-triphosphate (IP3) receptor antago- nist, heparin; the phospholipase C (PLC) inhibitor, U73122; and caffeine abolished mPSC or decreased mPSCs frequency. Calcium imaging showed that cytosolic Ca2+ was increased by thapsigargin and decreased by caffeine. These data demonstrate that internal store-released Ca2+ regulated by the PLC/IP3/IP3-receptor pathway has critical contribution to generation and control of miniature release in retinal ganglion cells.

Dry age-related macular degeneration (AMD), a multifactorial progressive degenerative disease of the retinal photoreceptors, pigmented epithelium and Bruch's membrane/choroid in central retina, causes visual impairment in millions of elderly people worldwide. The only available therapy for this disease is the over-the-counter (OTC) multi-vitamins plus macular xanthophyll (lutein/zeaxanthin) which attempts to block the damages of oxidative stress and ionizing blue light. Therefore development of dry AMD prescribed treatment is a pressing unmet medical need. However, this effort is currently hindered by many challenges, including an incomplete understanding of the mechanism of pathogenesis that leads to uncertain targets, confounded by not yet validated preclinical models and the difficulty to deliver the drugs to the posterior segment of the eye. Additionally, with slow disease progression and a less than ideal endpoint measurement method, clinical trials are necessarily large, lengthy and expensive. Increased commitment to research and development is an essential foundation for dealing with these problems. Innovations in clinical trials with novel endpoints, nontraditional study designs and the use of surrogate diseases might shorten the study time, reduce the patient sample size and consequently lower the budget for the development of the new therapies for the dry AMD.

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