Bax and Bcl-2 proteins closely interact with the component forming the mitochondria permeability transition pore that allows proteins to escape from mitochondria into cytosol to initiate apoptosis. In the current study, UVB irradiation resulted in ROS accumulation, an increase in Bax and a decrease in Bcl-2 besides mitochondrial membrane potential loss and caspase-3 activation as revealed by our previous findings. Excessive activity of NMDA-type glutamatergic channels has been implicated as a mechanism for neuronal injury in neurologic disorders, including glaucoma. Previous studies have demonstrated that intravitreal injection of NMDA resulted in significantly increased number of apoptotic RGCs and exogenous PACAP is able to counteract NMDA-induced toxicity. Since neural retinal degeneration induced by NMDA has been well established as an experimental glaucoma model, we adopted this model to investigate the protective effects of CHC. ERG has been considered as a more sensitive method to illustrate retinal injury than histology. The amplitude of PhNR is well recognized as a marker to reflect the function of RGCs. The b-wave mainly originates from bipolar cells that are post synaptic to photoreceptors. Reduced amplitudes in bwave and OPs are VE-821 commonly seen in the early stage of retinopathy even before its onset. With CHC administration, the amplitude of PhNR was increased from 1/3 to approximately 2/3 of the controls compared to eyes treated with NMDA only, suggesting marked recovery of RGC function. The functional outcomes, though not absolutely parallel with the morphological observation. Our morphometric analysis showed that intravitreal injection of CHC at different concentrations results in less cell loss in GCL. It was reported that the neuroprotection conferred by PACAP in NMDA-induced mice retinal damage was optimal at 100 pM increasing GCL cell number by about 16% of control, while no bimodal response was observed. In our studies, the protective effect of CHC on the retina is not strongly dose-dependent, with optimal effects acquired at 10 mM and 10 pM respectively, increasing GCL cell number by around 20% of control. Similarly, it has been reported that in transient ischemia model induced by high ocular pressure in rats, the neuroprotective effect of PACAP is bimodal with a concentration peak of 10 fM related to the MAP kinase cascade and another peak of 10 to 100 pM reflecting the cAMP cascade. The neuroprotective effect of PACAP in neuronal/astroglial cultures is also bimodal, with peak effects observed at a subpicomolar and a nanomolar concentration. Emerging evidence suggests that nanomolar concentrations of PACAP affect neurons directly, while subpicomolar concentrations exert an indirect glial-cell-mediated protective effect. Our results regarding the bimodal effect of CHC in the retina may suggest the involvement of two different pathways. Due to the difference in animal type and NMDA dosage, the results in the current studies aren’t quite comparable to previous ones where NMDA amount ranged from 5 nmol to 200 nmol and animal type varied between C57BL/6 mice and SD rats.