Comparison of retinal parameters between rhesus and cynomolgus macaques

Abstract

Nonhuman primates are important research models for basic vision research, preclinical pathogenesis, and treatment studies due to strong similarities in retinal structure and function with humans. We compared retinal parameters between 10 healthy normal rhesus macaques (Macaca mulatta) and 10 cynomolgus macaques (Macaca fascicularis) by optical coherence tomography and electroretinography. The Heidelberg Spectralis® HRA+OCT and Roland multifocal electrophysiometer were used to analyze retinal morphology, multifocal electroretinograms (mfERGs), and full-field electroretinograms (ff-ERGs). Mean retinal thickness was lowest in the central fovea of macaques and did not differ significantly between species, but the retinal thicknesses of the nerve fiber ganglion cell layer and the inner plexiform layer were significantly different. The amplitude density of the N1 wave was lower in rhesus macaques than in cynomolgus macaques in ring and quadrant areas. Dark-adapted 3.0 oscillatory potentials (reflection of amacrine cell activity) and light-adapted 30-hz flicker ERG (a sensitive cone-pathway-driven response) waveforms of the ff-ERG were similar in both species, while the times to peaks in dark-adapted 0.01 ERG (the rod-driven response of bipolar cells) and dark-adapted 3.0 ERG (combined rod and cone system responses) as well as the implicit times of the a- and b-waves in light-adapted 3.0 ERG (the single-flash cone response) were substantially different. This study provides normative retinal parameters for nonhuman primate research on basic and clinical ophthalmology, as well as a reference for researchers in the appropriate selection of rhesus or cynomolgus macaques as models for ophthalmology studies.

Keywords: cynomolgus macaques; electroretinogram; macula; retina; rhesus macaques.

Fig. 1.

Optical coherence tomography. A. Depiction of the standard 9 ETDRS (Early Treatment Diabetic Retinopathy Study) subfields. The topographic map for retinal thickness in the nine ETDRS subfields has a “horseshoe shape”. CSF, central subfield; IIM, inferior inner macula; IOM, inferior outer macula; NIM, nasal inner macula; NOM, nasal outer macula; SIM, superior inner macula; SOM, superior outer macula; TIM, temporal inner macula; TOM, temporal outer macula. B-D. Bar graphs of Retinal thicknesses in various regions of rhesus and cynomolgus macaques. **P<0.01, ***P<0.001.

Fig. 2.

Representative ff-ERG waveforms of rhesus and cynomolgus macaques. A, B. Dark-adapted 0.01 ERG waveforms of the two species, C. Bar graph of amplitude (Amp) and time to peak (t) in A and B. D, E. Dark-adapted 3.0 ERG waveforms. F. Bar graph of a-wave and b-wave amplitudes (a-amp, b-amp), time to trough (t1), and time to peak (t2) in D and E. G, H. Dark-adapted 3.0 OPs waveforms, I. Bar graph of amplitude and time to peak in G and H. J, K. Light-adapted 3.0 ERG waveforms. L. Bar graph of a-wave and b-wave amplitudes, time to trough, and time to peak in J and K. M, N. Light-adapted 30 Hz flicker ERG waveforms. O. Bar graph of amplitude and time to peak in M and N. Bold arrowheads indicate the stimulus flash. Solid arrows illustrate a-wave and b-wave amplitudes. Dotted arrows illustrate how time to trough and time to peak (t1, trough time; t2, implicit time or peak time) were measured. Ns P>0.05, **P<0.01, ***P<0.001.

Fig. 3.

Schematic diagram. A. Four ring regions in the macula. B. Four quadrant regions in the macula.