Effect of the Notch signaling pathway on retinal ganglion cells and its neuroprotection in rats with acute ocular hypertension

AIM： To explore the effect of the Notch signaling pathway on retinal ganglion cells（RGCs） and optic nerve in rats with acute ocular hypertension（OH）.METHODS： Totally 48 Sprague-Dawley（SD） rats were included, among which 36 rats were selected to establish acute OH models. OH rats received a single intravitreal injection of 2 μL phosphate buffered solution（PBS） and another group of OH rats received a single intravitreal injection of 10 μmol/L γ-secretase inhibitor（DAPT）. Quantitative real-time polymerase chain reaction（qPCR） and Western blot assay were adopted to determine the mRNA level of Notch and the protein levels of Notch, Bcl-2, Bax, caspase-3, and growth-associated protein 43（GAP-43）. The RGC apoptosis conditions were assessed by TUNEL staining.RESULTS： The OH rats and PBS-injected rats had increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, with severer macular edema and RGCs more loosely aligned, when compared with the normal rats. The DAPT-treated rats displayed increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, in comparison with the OH rats and PBSinjected rats. RGCs were hardly observed and macular edema became severe in the DAPT-treated rat.CONCLUSION： The Notch signaling pathway may suppress the apoptosis of retinal ganglion cells and enhances the regeneration of the damaged optic nerves in rats with acute OH.

Reduction on OFF-responses of Electroretinogram in Monkeys with Long-term High Intraocular Pressure

Background： There are ON- and OFF-pathways in the normal vertebrate retina. Short- and long-flash electroretinogram （ERG） are suitable methods to observe the function of ON- and OFF-pathways in vivo, respectively. It is clear that high intraocular pressure （IOP） might cause dysfunction of cone-dominated photopic negative response （PhNR） in monkeys with high lOP in ON-pathway. However, whether cone-dominated OFF-responses are also affected is less known. The aim of this study was to observe photopic OFF-responses of ERG in monkeys with high lOP. Methods： Nine monkeys were involved in the experiment from January 2006 to December 2016. High IOP was induced in the right eye by laser coagulation of the mid-trabecular meshwork in five monkeys. Six years after the laser coagulation, both short- and long-flash of the photopic ERG were recorded. Stimulus light was red flashes superimposed on a blue background. Four normal monkeys were examined under the same ERG protocols as controls. Paired t-test was used to compare the difference of each ERG parameter between the lasered eye and the fellow eye. Analysis of variance （ANOVA） with Tukey adjustment was adopted to calculate the differences among the lasered eye, the fellow eye, and the eyes of normal monkeys. Results： The mean amplitude of a-wave （11.73 ± 2.05） and PhNR （8.67 ± 2.44） in lasered eyes was significantly lower than that of a-wave （21.47 ±3.15） and PhNR （22.05 ± 3.42） in fellow eyes （P = 0.03 and P 0.01, respectively） in response to short flash. The mean amplitude old-wave （ 1.60 ± 0.59） and/-wave （3.13± 0.64） was significantly reduced in the lasered eyes than that of d-wave （4.01 ± 0.56） and/-wave （8.79 ± 1.75） in the fellow eyes （P =0.02 and P = 0.02, respectively） in response to long flash. Conclusions： Reduced OFF-responses are recorded in monkeys with high IOP when dysfunction ofphotoreceptor is involved. The reduced OFF-responses to long-flash stimulus show evidence of anomalous retinal circuitry in glaucomatous retinopathy.