Macular white dot lesions with hyperreflective optical coherence tomography findings in cynomolgus and rhesus monkeys

We screened 28 female cynomolgus monkeys (CMs) and 25 female rhesus monkeys (RMs) for white dots (WDs) in the macula and detected several animals with WDs in colonies at the Shin Nippon Biomedical Laboratories, Ltd., Drug Safety Research Laboratories (SNBL) facility. To determine the functional and morphological characteristics of WDs, we conducted ophthalmological and pathological examinations on these animals.

Fundus examination, optical coherence tomography (OCT), and focal electroretinogram (f-ERG) were conducted for all animals. Histopathology and transmission electron microscopy were conducted for one representative adult CM with WDs.

In both CMs and RMs, individual differences were observed in the number of WDs in the macula (ranging from approximately 10 to 500 per eye). Hyperreflective granules were observed between the ellipsoid zone (EZ) and the retinal pigment epithelium (RPE) in OCT. Both CMs and RMs exhibited a significant increase in the thicknesses of the RPE and choroid in WD animals compared to their normal counterparts. In the f-ERG, significant decreases and/or tendencies toward decreases in amplitudes and increases in implicit times of both a- and b-waves were observed in animals with WDs. In pathology, diffuse vacuolization of the RPE cells with tiny granules was observed in the macula.

Based on the results of OCT and pathological examinations, it was suggested that animals with WDs can develop macular degeneration in the future. To assess their suitability as a model for precursor lesions of age-related macular degeneration, it is imperative to continue monitoring the animals used in the present study until they reach a more advanced age of approximately another 5-10 years.