Abstract
Purpose::
Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of retinal disorders such as macula degeneration and diabetic retinopathy, and when administered intravitreally in animals reproduces aspects of these disease states. This study examined the neurosensory and anatomical consequences of periodic administration of intravitreal VEGF in the primate eye.
Methods::
An intravitreal injection of 1.25µg / 50µl VEGF was delivered 1-2 mm above the OD fovea of 3 cynomolgus (3-4.5 kg) at 1, 7 and 15 weeks after a 22-gauge sham injection as part of a control arm of a study. The animals were euthanized 2 months after the final VEGF injection (23 weeks post-sham) and OU were paraffin-sectioned and stained with H&E. Color fundus photography (7 fields), fluorescein angiography, retinal OCT and OU flash ERGs (0.01, 1 cd.sec/m2) were done at 0, 3 and 7 days after each VEGF injection and prior to sacrifice. Data are presented as mean ± SD.
Results::
Transient retinal fluorescein leak, retinal edema and ERG amplitude (A-wave, B-wave, 30 Hz flicker) reductions occurred in response to each VEGF challenge. The magnitude of the responses increased with subsequent dosing. For example, at 1, 2, 7, 8, 15, 16 and 23 weeks follow-up, OCT center fovea retina thicknesses were 127 ± 9 µm, 150 ± 16 µm, 125 ± 4 µm, 462 ± 315 µm, 127 ± 11 µm, 968 ± 467 µm and 129 ± 15 µm respectively; corresponding A wave amplitudes @ 1 cd.sec/m2 were 87 ± 23 µV, 54 ± 6 µV, 80 ± 20 µV, 27 ± 20 µV, 55 ± 22 µV, 12 ± 12 µV and 24 ± 15 µV, respectively. Qualitative examination by brightfield microscopy showed thinning of the photoreceptor layer in both the macula and periphery and photoreceptor disorganization in the fovea.
Conclusions::
VEGF-induced transient macula edema can result in photoreceptor atrophy and ERG deficits in the primate eye.
Keywords: electroretinography: non-clinical • growth factors/growth factor receptors • retina: distal (photoreceptors, horizontal cells, bipolar cells)