Bridging Animal and Human Models of Exercise-induced Visual Rehabilitation

Study Overview
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Brief Summary
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This study will determine whether blood biomarker changes predict sight-saving benefits of exercise.

Detailed Description
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Investigators of the Atlanta VA Center for Visual and Neurocognitive Rehabilitation (CVNR) find a very high prevalence of blinding diseases in the aging Veteran population. There are few treatments for the disorders that threaten our Veterans' eyesight. The work proposed here is the first step in determining whether exercise can be used by aging Veterans as an inexpensive and self-controlled therapy for vision loss. In order to translate exercise therapy for vision into the clinic, the investigators need to identify biomarkers that can be used to predict visual benefits. Though human and animal studies show that aerobic exercise is beneficial to specific central and peripheral nervous system functions, effects on the retina and vision were unknown until the investigators recently discovered that treadmill exercise directly protects retinal neurons in mice undergoing light-induced retinal degeneration (LIRD). The investigators found that exercise increased levels of brain-derived neurotrophic factor (BDNF) a blood protein in the blood, brain and eyes, whereas treatment of mice with a BDNF inhibitor prevented the protective effects of exercise. For this study, the investigators will assess visual outcomes and serum biomarkers (e.g, BDNF) in 60 subjects age 18-89 before, during, and after aerobic exercise. Subjects currently enrolled in a 12-week study (under IRB 56726) examining the effects of aerobic exercise on cognition will have visual testing (ERG, visual acuity, contrast sensitivity, and OCT) and blood collection prior to, during and after the standardized 12-week aerobic exercise regimen to determine whether circulating biomarker levels and visual outcomes are correlated and whether biomarker levels are altered as predicted in animal studies. This study will determine whether biomarker changes predict sight-saving benefits of exercise. As opposed to surgery or pharmacological treatments, exercise programs provide a means for Veterans to exert some control over their visual disease progression and will increase their overall health.

Official Title
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Bridging Animal and Human Models of Exercise-induced Visual Rehabilitation

Conditions
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Vision Disorders

Intervention / Treatment
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* Behavioral: Aerobic exercise
* Behavioral: Balance exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: English speaking Aged 18 to 89 Sedentary as defined by < 120 min/week of aerobic exercise over prior 3 months Non-demented (MMSE 24) Exclusion Criteria: Severe diabetes requiring insulin Cognitive-executive function deficit (MoCA < 26)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aerobic Exercise<br>Exercise 3 times a week | Behavioral: Aerobic exercise<br>* Stationary bicycle ergometer @ 50-80% of maximal heart rate reserve for 20 minutes to 45 minutes<br>|
| Placebo Comparator: Balance Training<br>Group balance training 3 times a week | Behavioral: Balance exercise<br>* Instructor-led exercises done in a group setting for strengthening, balance, flexibility<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual acuity | Early Treatment Diabetic Retinopathy Study (ETDRS) chart | 12 weeks | 
| serum BDNF | Blood will be drawn prior to and after exercise sessions. From this, serum levels of brain derived neurotrophic factor (BDNF) will measured by immunoenzymatic assay. | 12 weeks | 
| Retinal morphology | Scanning laser ophthalmoscopy/optical coherence tomography (SLO/OCT) | 12 weeks | 
| Contrast sensitivity | CSV1000E Contrast Chart | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise, Retinal Degeneration, Neuropharmacology, Brain-Derived Neurotrophic Factor, Biometry, Immunochemistry, Molecular Biology, Neurosciences, Ophthalmology