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Retinal Amyloid Clearance Enhanced by 40-Hz Light Flicker via MHC-II+ Microglia Regulation in Mice
Wang Sheng1,2,3,4,5, Qichang Wang1,2, Yinhua Huang1,3
1Aier Academy of Ophthalmology, Central South University, Changsha, Hunan, China.
Purpose:
This study aimed to investigate whether 40-Hz light flicker could modulate the expression of major histocompatibility complex class II (MHC-II) and enhance the clearance of amyloid-β (Aβ) deposition.
Methods:
We examined retinal MHC-II expression via RNA sequencing, immunofluorescence, and western blotting in mice 8 weeks, 9 months, and 18 to 20 months old. Retinal metabolic waste accumulation was induced by intravitreal and subretinal injections of Aβ oligomers. The impact of 40-Hz flicker on MHC-II expression, microglial activation, and retinal function was evaluated using immunofluorescence, western blotting, dot immunobinding assay, electroretinography, and optokinetic reflex (OKR) testing. Minocycline was used to inhibit microglial activity.
Results:
The 40-Hz light flicker upregulated MHC-II expression in the retinas of aged mice. MHC-II⁺ microglia accumulated along retinal veins and exhibited increased numbers and enlarged morphology in the subretinal space. Following intravitreal or subretinal Aβ injection, 40-Hz flicker enhanced microglial activation, further upregulated MHC-II expression, promoted Aβ clearance, and improved electroretinogram responses and OKR performance. These effects were abolished by minocycline treatment.
Conclusions:
We observed that 40-Hz light flicker enhances retinal microglial clearance of Aβ oligomers by upregulating MHC-II expression. These findings support 40-Hz light flicker as a non-invasive therapeutic strategy for age-related retinal disorders by promoting metabolic waste clearance.
Insights
Forty-hertz light flicker therapy boosts major histocompatibility complex class II (MHC-II) expression in aged mouse retinas. This approach enhances microglial clearance of amyloid-beta (Aβ) deposits, offering a potential treatment for age-related retinal diseases.
Area of Science:
- Neuroscience
- Immunology
- Ophthalmology
Background:
- Age-related retinal disorders are often associated with metabolic waste accumulation, such as amyloid-beta (Aβ) deposits.
- Microglia play a crucial role in retinal immune surveillance and waste clearance.
- Major histocompatibility complex class II (MHC-II) is an important molecule involved in immune cell function and antigen presentation.
Purpose of the Study:
- To investigate the effect of 40-Hz light flicker on MHC-II expression in the retina.
- To determine if 40-Hz light flicker can enhance the clearance of Aβ deposition in the retina.
- To explore the potential of 40-Hz light flicker as a therapeutic strategy for age-related retinal disorders.
Main Methods:
- Retinal MHC-II expression was analyzed using RNA sequencing, immunofluorescence, and western blotting in mice of different ages.
- Aβ oligomers were injected intravitreally and subretinally to induce metabolic waste accumulation.
- The impact of 40-Hz flicker on microglial activation, Aβ clearance, and retinal function (electroretinography, optokinetic reflex) was assessed.
- Minocycline was administered to inhibit microglial activity.
Main Results:
- 40-Hz light flicker significantly upregulated MHC-II expression in aged mouse retinas.
- MHC-II-expressing microglia showed increased accumulation and altered morphology around retinal veins and in the subretinal space.
- 40-Hz flicker enhanced microglial activation, promoted Aβ clearance, and improved retinal function following Aβ injection.
- The beneficial effects of 40-Hz flicker were abrogated by minocycline treatment, indicating a role for microglia.
Conclusions:
- 40-Hz light flicker therapy upregulates retinal MHC-II expression and enhances microglial-mediated clearance of Aβ oligomers.
- This non-invasive approach shows promise for promoting metabolic waste clearance in age-related retinal diseases.
- 40-Hz light flicker represents a potential therapeutic strategy for improving retinal health in aging populations.
