Longitudinal retinal functional evaluation using full-field electroretinography in New Zealand white and Dutch Belted rabbits with aging

Abstract

Electroretinography (ERG) is pivotal in elucidating retinal function, yet investigations into the temporal dynamics of ERG signals in New Zealand White (NZW) and Dutch-belted (DB) rabbits remain scarce. This study presents a longitudinal assessment of retinal function in both NZW and DB strains. ERG recordings were conducted on four NZW and four DB rabbits at 2, 7, 15, and 24 months of age, encompassing both dark-adapted and light-adapted protocols at each time point. Quantitative analyses included assessment of a- and b-wave amplitudes, implicit times, and photopic flicker responses. Results revealed consistently stronger a- and b-wave amplitudes in NZW rabbits compared to DB rabbits across all time points. These stronger ERG responses likely result from increased effective light exposure at the photoreceptor level in NZW rabbits, rather than indicating intrinsic differences in retinal sensitivity. Over time, NZW rabbits showed a decline in visual function of the cone and postreceptoral systems, with the rod system less affected. In contrast, the visual function of DB rabbits initially improved at an early stage, followed by a slight decline after 15 months. The differences between the two strains may be attributed to the varying speeds of retinal maturation, melanin's absorption of light, and its protective effect against light-induced retinal damage. This dataset underscores the differential retinal characteristics between NZW and DB rabbits, shedding light on their distinct functional profiles.

Fig. 1

Multimodal imaging of New Zealand White (NZW) and Dutch-belted (DB) Rabbit retina: (A and E) Color fundus photography image of NZW (A) and DB (E) rabbits, respectively. These images clearly show morphology of retinal vessels (RVs), nerve fiber layer (NFL), choroidal vessels (CVs), retinal pigment epithelium (RPE), and optic nerve (white dotted circles). (B and F) Fundus autofluorescence images showing healthy retina without any evidence of RPE atrophy. (C and G) Fluorescein angiography of NZW and DB, respectively. (D and H) Indocyanine green angiography images clearly show structure of the choroidal vessels. (I and J) B-scan spectral domain OCT (SD-OCT) images demonstrating the cross section retina constructed from different layers such as inner limiting membrane (ILM), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor layer (PL), choroid layer (CL), and sclera. The OCT scan region of interest is indicated by scanning lines (SL) and marks as red dotted lines overlay on the fundus photographs (a and d), corresponding to the rabbit’s visual streak. This region was chosen for its high photoreceptor density and relevance to retinal function as a structure akin to the human macula.

Fig. 2

Comparison of rod responses in NZW and DB rabbits at different ages: (A) Representative rod ERG waveforms recorded to a scotopic 0.01 cd·s/m², flash under dark-adapted conditions in NZW and DB rabbits from 2 to 24 months of age. Scale bars = 30 ms (x-axis) and 200 µV (y-axis). (B) Raw B-wave amplitude and (C) implicit time of rod responses in NZW and DB rabbits over time. Horizontal bars = mean values; boxes = interquartile range; capped lines = standard deviation (n = 8, * P < 0.05, ** P < 0.01, *** P < 0.001).

Fig. 3

Comparison of combined rod and cone responses in NZW and DB rabbits at different ages: (A) Representative combined rod and cone ERG waveforms recorded to a scotopic 3.0 cd·s/m², flash under dark-adapted conditions in NZW and DB rabbits from 2 to 24 months of age. Scale bars = 30 ms (x-axis) and 200 µV (y-axis). (B) Raw A-wave amplitude, (C) B-wave amplitude, (D) A-wave implicit time, and (E) B-wave implicit time of scotopic combined rod and cone responses in NZW and DB rabbits over time. Horizontal bars = mean values; boxes = interquartile range; capped lines = standard deviation (n = 8, *P < 0.05, **P < 0.01, ***P < 0.001).

Fig. 4

Comparison of photopic responses in NZW and DB rabbits at different ages: (A) Representative ERG waveforms recorded to a photopic 3.0 cd·s/m², flash under light-adapted conditions in NZW and DB rabbits from 2 to 24 months of age. Scale bars = 30 ms (x-axis) and 200 µV (y-axis). (B) Raw A-wave amplitude, (C) B-wave amplitude, (D) A-wave implicit time, and (E) B-wave implicit time of photopic responses in NZW and DB rabbits over time. Horizontal bars = mean values; boxes = interquartile range; capped lines = standard deviation (n = 8, *P < 0.05, ***P < 0.001).

Fig. 5

Comparison of cone responses in NZW and DB rabbits at different ages: (A) Representative ERG waveforms recorded to a photopic 3.0 cd·s/m², 30 Hz flash under light-adapted conditions in NZW and DB rabbits from 2 to 24 months of age. Scale bars = 30 ms (x-axis) and 100 µV (y-axis). (B) Raw amplitude and (C) implicit time of cone responses in NZW and DB rabbits over time. A significant difference between strains was observed only at 7 months (P < 0.05). Horizontal bars = mean values; boxes = interquartile range; capped lines = standard deviation (n = 8, * P < 0.05, **P < 0.01, ***P < 0.001).