Neuroprotective effects of exogenous brain-derived neurotrophic factor on amyloid-beta 1-40-induced retinal degeneration

Amyloid-beta(Aβ)-related alterations,similar to those found in the brains of patients with Alzheimer's disease,have been observed in the retina of patients with glaucoma.Decreased levels of brain-derived neurotrophic factor(BDNF)are believed to be associated with the neurotoxic effects of Aβpeptide.To investigate the mechanism underlying the neuroprotective effects of BDNF on Aβ_(1-40)-induced retinal injury in Sprague-Dawley rats,we treated rats by intravitreal administration of phosphate-buffered saline(control),Aβ_(1-40)(5 nM),or Aβ_(1-40)(5 nM)combined with BDNF(1μg/mL).We found that intravitreal administration of Aβ_(1-40)induced retinal ganglion cell apoptosis.Fluoro-Gold staining showed a significantly lower number of retinal ganglion cells in the Aβ_(1-40)group than in the control and BDNF groups.In the Aβ_(1-40)group,low number of RGCs was associated with increased caspase-3 expression and reduced TrkB and ERK1/2 expression.BDNF abolished Aβ_(1-40)-induced increase in the expression of caspase-3 at the gene and protein levels in the retina and upregulated TrkB and ERK1/2 expression.These findings suggest that treatment with BDNF prevents RGC apoptosis induced by Aβ_(1-40)by activating the BDNF-TrkB signaling pathway in rats.

Suprachoroidal injection of ketorolac tromethamine does not cause retinal damage

Rabbit right eyes were injected with 3 or 6 mg ketorolac tromethamine into the suprachoroidal space. Electroretinography results demonstrated no abnormal changes in rod cell response, maximum rod cell or cone cell mixing reaction, oscillation potential, cone cell response, waveform, amplitude, and potential of 30 Hz scintillation response in right eyes before injection, and at 1,2, and 4 weeks after injection. There was no difference between left （control） and right eyes. Under light microscopy, the histomorphology of cells in each retinal layer was normal at 4 weeks following 6 mg ketorolac tromethamine administration. These results indicate that a single suprachoroidal injection of 3 or 6 mg ketorolac tromethamine into rabbits was safe. Suprachoroidal space injection appears to be safe.

Safety of intravitreal quinupristin/dalfopristin in an animal model

AIM： To determine whether different intravitreal doses of quinupristin/dalfopristin lead to electroretinographic or histological changes in the rabbit retina over one month period after injection. METHODS： Eighteen New Zealand white rabbits were divided into three treatment groups （groups 1 to 3） and different intravitreal doses of quinupristin/dalfopristin were tested in each group. The right eye was injected with the drug and the left eye received intravitreal injection of 5% dextrose water and served as control eye. The doses delivered to each group were 0.1 mg/0.1 mL, 1 mg/0.1 mL and 10 mg/0.1 mL. Simultaneous, bilateral, dark-adapted electroretinography and clinical images of both eyes were obtained in all groups before injection （baseline） and after 7, 14, 21 and 28d, followed by enucleation for histological examination. RESULTS： Subjects in the group 1 showed no signs of toxicity in the electroretinogram when compared with groups 2 and 3 （Kruskall-Wallis test, P=0.000）. By day 7, no electrical response to light stimuli was recorded in the treated eyes in groups 2 and 3, consistent with severe damage due to retinal toxicity. Light microscopy revealedno significant histopathological changes in the group 1, while rabbits in groups 2 and 3 had signs of granulomatous inflammation in most cases. CONCLUSION： Intravitreal 0.1 mg/0.1 mL doses of quinupristin/dalfopristin do not lead to electroretinographic or histological signs of retinal toxicity compared with 1 mg/0.1 mL and 10 mg/O.1 mL in this rabbit model.