1. Research Background

The normal function of retinal cells requires an adequate supply of oxygen and metabolic nutrients. A well-developed retinal vascular system possesses intrinsic regulatory capacity, enabling it to modulate blood flow and perfusion pressure in response to changes in the metabolic demands of the tissue. It is widely accepted that flicker light stimulation enhances retinal activity, and the accompanying increase in blood flow provides more oxygen and nutrients to the retina to meet its elevated metabolic requirements. Previous studies have shown that in pathological conditions such as diabetic retinopathy and age-related macular degeneration, the flicker light-induced vasodilation response is significantly attenuated. However, research on the changes in retinal blood flow (RBF) induced by flicker light stimulation (FLS) following retinal ischemia-reperfusion injury remains limited.

Earlier studies have demonstrated that transient flicker light stimulation (FLS) enhances retinal blood flow (RBF) and full-field electroretinogram (ffERG) responses in wild-type mice. This study aims to investigate the impact of acute ocular hypertension (AOH) on the aforementioned flicker light-induced effects in mice.

2. Methods

Adult C57BL/6J mice were randomly divided into three groups: the acute ocular hypertension (AOH) group, the sham-operated (sham) group, and the naïve control (naïve) group. All experimental animals underwent the following assessments at baseline (Day 0), Day 16, and Day 43: scotopic and photopic full-field electroretinography (measured before and after 12 Hz flicker light stimulation), optical coherence tomography (OCT), and Doppler optical coherence tomography (measured before and after 12 Hz flicker light stimulation).

On Day 8 (eight days after baseline measurements), intraocular pressure (IOP) in the AOH group was elevated to 80 mmHg and maintained for one hour via anterior chamber cannulation. The sham group underwent the same surgical procedure, but IOP was maintained at 15 mmHg in one randomly selected eye. Animals in the naïve group were only transported to the operating table, anesthetized, and left on the table for 60 minutes to acclimate to the surgical environment; unlike the AOH and sham groups, they received no experimental intervention. IOP measurements in both the AOH and sham groups were performed using a TonoLab rebound tonometer (Icare Finland Oy, Helsinki, Finland) specifically designed for rodents.

3. Results

At baseline (Day 0), transient flicker light stimulation (FLS) significantly increased retinal blood flow (RBF) and photopic b-wave amplitudes in all three groups of mice.

On Days 16 and 43, the positive scotopic threshold response and the thickness of the inner and middle retinal layers were significantly reduced in the acute ocular hypertension (AOH) group.

In the sham-operated and naïve control groups, significant FLS-induced increases in RBF and b-wave amplitude were still observable on Days 16 and 43. However, compared to these two groups, the AOH group exhibited a significantly attenuated enhancement of both RBF and b-wave amplitude in response to flicker light stimulation.

4. Conclusion

Acute ocular hypertension (AOH) impairs the enhancement of retinal blood flow (RBF) and electroretinographic responses induced by flicker light stimulation. This impairment suggests that functional hyperemia in the retina is highly sensitive to elevated intraocular pressure.

Milan Rai; Kaiyip Choi; Henry Ho-lung Chan

iOVS Investigative Ophthalmology & Visual Science 

February 2026, Vol.67, 33. 

doi:https://doi.org/10.1167/iovs.67.2.33

https://iovs.arvojournals.org/article.aspx?articleid=2811491&resultClick=1