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Biobanking of Human Aqueous and Vitreous Liquid Biopsies for Molecular Analyses
Published on: September 11, 2023
Molecular medicine in ophthalmic care
Stuart Richer1, William Stiles, Carla Thomas
1Eye Clinic, Department of Veterans Affairs Medical Center, North Chicago, Illinois, USA. Stuart.Richer1@VA.Gov
Background:
Lipofuscin is the most consistent and phylogenically constant morphologic marker of cellular aging. Autofluorescence of the A2E fluorophore within retinal pigment epithelial (RPE) lipofuscin affords the opportunity for noninvasive evaluation of age- and disease-related pathophysiological changes in the human retina. It is being used in National Eye Institute/Age-Related Eye Disease Study II to evaluate age-related macular degeneration (AMD) geographic atrophy expansion. Experiments show lipofuscin can be reversed in cell culture and animal models in heart, brain, spinal cord, and retinal tissues, using an array of antioxidants and iron chelators.
Methods:
An 80-year-old man with a gastric resection presented with complaints of unremitting night driving difficulty despite treatment with lutein and omega III fatty acids. Notable parafoveal deposition of retinal lipofuscin by 50 degrees fundus auto-fluorescence (580 nm excitation/660 barrier filters) and concurrent abnormalities in non-Snellen measures of visual function-Contrast Sensitivity Function, 6.5 degrees large field tritan threshold, 10 degrees threshold visual fields, and deficits in the National Institutes of Health/National Eye Institute Visual Function Questionnaire (VFQ) 25 subjective night driving/mental health subscale questionnaire were obtained. The patient was placed on an over-the-counter daily oral polyphenolic mixture containing resveratrol and re-evaluated 5 months later.
Results:
The data reveal improvements in all measures of visual function, subjective improvement in vision and mental functioning on the VFQ 25, and visible clearing of RPE lipofuscin.
Conclusion:
To our knowledge, we believe this to be the first reported human clinical case of lipofuscin reversal in the human eye correlated with measured clinical and subjective improvement in visual and mental function after nutraceutical intervention.
Insights
Cellular aging marker lipofuscin, a hallmark of retinal pigment epithelial (RPE) cells, was reversed in an 80-year-old man using a nutraceutical. This reversal correlated with improved vision and mental function.
Area of Science:
- Ophthalmology
- Cellular Biology
- Gerontology
Background:
- Lipofuscin, a cellular aging marker, accumulates in retinal pigment epithelial (RPE) cells.
- Autofluorescence of lipofuscin's A2E fluorophore aids in evaluating retinal aging and disease.
- Previous studies demonstrated lipofuscin reversal in animal models and cell cultures.
Observation:
- An 80-year-old man with night driving difficulties showed significant RPE lipofuscin deposition.
- Visual function tests revealed deficits in contrast sensitivity and visual fields.
- Patient reported subjective visual and mental health decline.
Findings:
- Nutraceutical intervention with a polyphenolic mixture containing resveratrol was administered.
- Five months later, significant improvements were observed in all visual function measures.
- Subjective reports indicated enhanced vision and mental functioning, alongside visible clearing of RPE lipofuscin.
Implications:
- This case report presents the first human clinical evidence of lipofuscin reversal in the eye.
- Nutraceutical intervention may offer a novel approach to managing age-related visual and cognitive decline.
- Further research is warranted to explore the therapeutic potential of lipofuscin reversal.
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