Development of Microcystoid Macular Degeneration in the Retina of Nonhuman Primates: Time-Course and Associated
Thomas C M Lavery1, Carol A Rasmussen1,2, Alexander W Katz1,2
1Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Purpose:
Microcystoid macular degeneration (MMD) is a condition where cystoid vacuoles develop within the inner nuclear layer of the retina in humans in a variety of disorders. Here we report the occurrence of MMD in non-human primates (NHPs) with various retinal ganglion cell (RGC) pathologies and evaluate the hypothesis that MMD does not precede RGC loss but follows it.
Methods:
Morphological studies were performed of the retinas of NHPs, specifically both rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis), in which MMD was identified after induction of experimental glaucoma (EG), hemiretinal endodiathermy axotomy (HEA), and spontaneous idiopathic bilateral optic atrophy. In vivo imaging analyses included fundus photography, fluorescein angiography (FA), optical coherence tomography (OCT), adaptive optics scanning laser ophthalmoscopy (AOSLO), light microscopy, and electron microscopy.
Results:
MMD, like that seen on OCT scans of humans, was found in both rhesus and cynomolgus macaques with EG. Of 13 cynomolgus macaques with chronic EG imaged once with OCT six of 13 animals were noted to have MMD. MMD was also evident in a cynomolgus macaque with bilateral optic atrophy. Following HEA, MMD did not develop until at least 2 weeks following the RNFL loss.
Conclusion:
These data suggest that MMD may be caused by a retrograde trans-synaptic process related to RGC loss. MMD is not associated with inflammation, nor would it be an independent indicator of drug toxicity per se in pre-clinical regulatory studies. Because of its inconsistent appearance and late development, MMD has limited use as a clinical biomarker.
Insights
Microcystoid macular degeneration (MMD) in non-human primates follows retinal ganglion cell (RGC) loss, suggesting a retrograde process. MMD is not an early indicator of RGC damage or drug toxicity.
Area of Science:
- Ophthalmology
- Neuroscience
- Primate Research
Background:
- Microcystoid macular degeneration (MMD) involves cystoid vacuoles in the retina's inner nuclear layer.
- MMD is observed in various human retinal disorders.
Purpose of the Study:
- Investigate MMD occurrence in non-human primates (NHPs) with retinal ganglion cell (RGC) pathologies.
- Test the hypothesis that MMD follows RGC loss, rather than preceding it.
Main Methods:
- Morphological analysis of retinas from rhesus and cynomolgus macaques.
- Induction of experimental glaucoma (EG), hemiretinal endodiathermy axotomy (HEA), and observation of optic atrophy.
- In vivo imaging including OCT, FA, and AOSLO; light and electron microscopy.
Main Results:
- MMD was observed in NHPs with EG, similar to human OCT findings.
- MMD developed at least two weeks after retinal nerve fiber layer (RNFL) loss in HEA models.
- MMD was also present in a macaque with bilateral optic atrophy.
Conclusions:
- MMD likely results from a retrograde trans-synaptic process secondary to RGC loss.
- MMD is not linked to inflammation or drug toxicity in preclinical studies.
- MMD's late onset and inconsistent appearance limit its utility as a clinical biomarker.
