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Among the deficits in visual processing that accompany healthy aging, the earliest originate in the retina. Moreover, sex-related differences in retinal function have been increasingly recognized. To better understand the dynamics of the retinal aging trajectory, we used the light-adapted flicker electroretinogram (ERG) to functionally assess the state of the neuroretina in a large cohort of age- and sex-matched vervet monkeys (N = 35), aged 9 to 28 years old, with no signs of obvious ocular pathology. We primarily isolated the cone-bipolar axis by stimulating the retina with a standard intensity light flash (2.57 cd/s/m(2)) at eight different frequencies, ranging from 5 to 40 Hz. Sex-specific changes in the voltage and temporal characteristics of the flicker waveform were found in older individuals (21-28 years-old, N = 16), when compared to younger monkeys (9-20 years-old, N = 19), across all stimulus frequencies tested. Specifically, significantly prolonged implicit times were observed in older monkeys (p < 0.05), but a significant reduction of the amplitude of the response was only found in old male monkeys (p < 0.05). These changes might reflect ongoing degenerative processes targeting the retinal circuitry and the cone subsystem in particular. Altogether, our findings corroborate the existing literature in humans and other species, where aging detrimentally affects photopic retinal responses, and draw attention to the potential contribution of different hormonal environments.

The expression of the endocannabinoid (eCB) system, including cannabinoid receptor type 1 (CB1R) and the cannabinoid synthesizing (NAPE-PLD) and degrading (FAAH) enzymes, has been well-characterized in the retina of rodents and monkeys. More recently, the presence of CB1R was localized throughout the dorsal lateral geniculate nucleus of the thalamus of vervet monkeys. Given that the retina projects also to the pulvinar either via a direct projection or via the superior colliculus, it was reasonable to assume that this system would be present therein. The visual pulvinar, namely the inferior pulvinar (PI) region, was delineated with calbindin immunohistochemical staining. Using Western blots and immunofluorescence, we demonstrated that CB1R, NAPE-PLD and FAAH are expressed in the PI of the vervet monkey. Throughout the PI, CB1R was mainly colocalized with VGLUT2-positive axon terminals in the vicinity of calbindin and parvalbumin-positive neurons. NAPE-PLD and FAAH rather colocalized with calbindin over the somatodendritic compartment of PI neurons. Our results suggest that visual information coming from the retina and entering the PI is modulated by the eCB system on its way to the dorsal visual stream. These results provide insights for understanding the role of eCBs in the modulation of visual thalamic inputs and, hence, visual perception.

The endogenous cannabinoid system plays important roles in the retina of mice and monkeys via their classic CB1 and CB2 receptors. We have previously reported that the G protein-coupled receptor 55 (GPR55), a putative cannabinoid receptor, is exclusively expressed in rod photoreceptors in the monkey retina, suggesting its possible role in scotopic vision. To test this hypothesis, we recorded full-field electroretinograms (ERGs) after the intravitreal injection of the GPR55 agonist lysophosphatidylglucoside (LPG) or the selective GPR55 antagonist CID16020046 (CID), under light- and dark-adapted conditions. Thirteen vervet monkeys (Chlorocebus sabaeus) were used in this study: four controls (injected with the vehicle dimethyl sulfoxide, DMSO), four injected with LPG and five with CID. We analyzed amplitudes and latencies of the a-wave (photoreceptor responses) and the b-wave (rod and cone system responses) of the ERG. Our results showed that after injection of LPG, the amplitude of the scotopic b-wave was significantly higher, whereas after the injection of CID, it was significantly decreased, compared to the vehicle (DMSO). On the other hand, the a-wave amplitude, and the a-wave and b-wave latencies, of the scotopic ERG responses were not significantly affected by the injection of either compound. Furthermore, the photopic ERG waveforms were not affected by either drug. These results support the hypothesis that GPR55 plays an instrumental role in mediating scotopic vision.