A2E and lipofuscin distributions in macaque retinal pigment epithelium are similar to human
Patrick Pallitto1, Zsolt Ablonczy, E Ellen Jones
1Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, USA. ablonczy@musc.edu.
Abstract:
The accumulation of lipofuscin, an autofluorescent aging marker, in the retinal pigment epithelium (RPE) has been implicated in the development of age-related macular degeneration (AMD). Lipofuscin contains several visual cycle byproducts, most notably the bisretinoid N-retinylidene-N-retinylethanolamine (A2E). Previous studies with human donor eyes have shown a significant mismatch between lipofuscin autofluorescence (AF) and A2E distributions. The goal of the current project was to examine this relationship in a primate model with a retinal anatomy similar to that of humans. Ophthalmologically naive young (<10 years., N = 3) and old (>10 years., N = 4) Macaca fascicularis (macaque) eyes, were enucleated, dissected to yield RPE/choroid tissue, and flat-mounted on indium-tin-oxide-coated conductive slides. To compare the spatial distributions of lipofuscin and A2E, fluorescence and mass spectrometric imaging were carried out sequentially on the same samples. The distribution of lipofuscin fluorescence in the primate RPE reflected previously obtained human results, having the highest intensities in a perifoveal ring. Contrarily, A2E levels were consistently highest in the periphery, confirming a lack of correlation between the distributions of lipofuscin and A2E previously described in human donor eyes. We conclude that the mismatch between lipofuscin AF and A2E distributions is related to anatomical features specific to primates, such as the macula, and that this primate model has the potential to fill an important gap in current AMD research.
Insights
Lipofuscin and bisretinoid A2E distributions do not correlate in primate retinas, similar to human findings. This mismatch, linked to primate-specific anatomy like the macula, is crucial for age-related macular degeneration research.
Area of Science:
- Ophthalmology
- Retinal Biology
- Aging Research
Background:
- Lipofuscin accumulation in the retinal pigment epithelium (RPE) is linked to age-related macular degeneration (AMD).
- Lipofuscin contains bisretinoid N-retinylidene-N-retinylethanolamine (A2E), a key visual cycle byproduct.
- Previous human studies revealed a spatial mismatch between lipofuscin autofluorescence and A2E distribution.
Purpose of the Study:
- To investigate the relationship between lipofuscin and A2E distributions in a primate model.
- To compare lipofuscin and A2E spatial patterns in Macaca fascicularis (macaque) retinas to human findings.
- To assess the utility of a primate model for age-related macular degeneration research.
Main Methods:
- Sequential fluorescence and mass spectrometric imaging of RPE/choroid tissue from young and old macaque eyes.
- Flat-mounting of RPE/choroid tissue on conductive slides for imaging.
- Comparative analysis of lipofuscin autofluorescence and A2E distributions.
Main Results:
- Lipofuscin autofluorescence intensity peaked in a perifoveal ring in primate RPE.
- A2E levels were consistently highest in the retinal periphery.
- A significant lack of correlation between lipofuscin and A2E distributions was confirmed in the primate model.
Conclusions:
- The observed mismatch between lipofuscin autofluorescence and A2E is attributed to primate-specific anatomical features, including the macula.
- The macaque model effectively replicates the human lipofuscin-A2E distribution mismatch.
- This primate model offers a valuable tool for advancing age-related macular degeneration research.
