New research from the University of Southampton, England is investigating the mechanisms that contribute to the development of age-related macular degeneration (AMD) – particularly the presence of the beta-amyloid proteins that also accumulate in the brains of people with Alzheimer’s disease.
According to study co-author Arjuna Ranayaka, Ph.D., “We know that AMD is caused by a combination of genetic, environmental, and lifestyle risk factors, but this novel discovery could open up new possibilities to understand how the aging retina becomes damaged. Such advances are important if we are to develop better AMD treatments in the future.”
Please note that this research does not indicate that age-related macular degeneration can result from Alzheimer’s disease, or that one condition can contribute to the development of the other. What the research does indicate, however, is that studying the behavior of Alzheimer’s-related beta-amyloid proteins can provide insight into the retinal damage that accompanies macular degeneration.
From Experimental Eye Research
This new research regarding the potential role of beta-amyloid protein (explained below) in the development of macular degeneration has been published in the December 2016 edition of Experimental Eye Research. The primary goal of Experimental Eye Research is to publish original research on all aspects of experimental biology of the eye and ocular tissues “that seek to define the mechanisms of normal function and/or disease.”
The authors are George Taylor-Walker, Savannah A. Lynn, Eloise Keeling, Rosie Munday, David A. Johnston, Anton Page, Jennifer A. Scott, Srini Goverdhan, Andrew J. Lotery, and J. Arjuna Ratnayaka, from the University of Southampton and the University Hospital Southampton NHS Foundation Trust, United Kingdom.
What is Beta-Amyloid?
In its most basic form, beta-amyloid (BAY-tuh AM-uh-loyd) is a single protein fragment, snipped from a larger protein found in the fatty membrane surrounding nerve cells. Because it is chemically “sticky,” these protein fragments tend to clump or cluster, gradually building into hard, insoluble “plaques” in the brain that are one of the hallmarks of Alzheimer’s disease. As they cluster, these beta-amyloid plaques erode synapses, which are the connections between nerve cells that help to conduct nerve impulses. Synapses are essential in encoding, consolidating, storing, and retrieving memories.
However, there is much that is still unknown about beta-amyloid, as evidenced by the discouraging results of a recent clinical trial for an experimental drug targeting amyloid buildup in patients with Alzheimer’s disease. According to the New York Times,
An experimental Alzheimer’s drug that had previously appeared to show promise in slowing the deterioration of thinking and memory has failed in a large Eli Lilly clinical trial, dealing a significant disappointment to patients hoping for a treatment that would alleviate their symptoms.
The failure of the drug, solanezumab, underscores the difficulty of treating people who show even mild dementia, and supports the idea that by that time, the damage in their brains may already be too extensive. And because the drug attacked the amyloid plaques that are the hallmark of Alzheimer’s, the trial results renew questions about a leading theory of the disease, which contends that it is largely caused by amyloid buildup.
No drug so far has been able to demonstrate that removing or preventing the accumulation of amyloid translates into a result that matters for patients: stalling or blocking some of the symptoms of dementia.
About the Macular Degeneration/Amyloid Research
Excerpted from Macular degeneration: Study sheds light on Alzheimer’s proteins in retina, via Medical News Today:
For their study, [the researchers] used cell cultures and mouse models of macular degeneration (AMD) to investigate mechanisms of Alzheimer’s beta-amyloid accumulation inside retinal cells. They were particularly interested in the speed with which the amyloid proteins find their way inside the retinal cells.
The researchers found the retinal cells internalized the amyloid proteins within 24 hours of being exposed to them.
They also discovered that the amyloid proteins are retained inside the retinal cells, where they gradually impair a molecular mechanism reliant on the protein encoded by the MAP-2 gene. Among other things, MAP-2 mechanisms help to maintain important structures inside cells called microtubules.
[Study co-author] Dr. Arjuna Ratnayaka says they were surprised at the speed with which the amyloid proteins entered the cells, and he suggests the finding may help explain how a healthy retina can switch to a diseased, AMD retina.
The team plans to continue its research, particularly assessing how the amyloid beta proteins penetrate retinal cells and begin to cause internal damage – beginning the framework for preventative options or treatment methods. The hope is that the continuing work will lead to measures to prevent or treat AMD.
More Information about Age-Related Macular Degeneration
Age-related macular degeneration (AMD) is a gradual, progressive, painless deterioration of the macula, the small sensitive area in the center of the retina that provides clear central vision. Damage to the macula impairs the central (or “detail”) vision that helps with essential everyday activities, such as reading and writing, preparing meals, watching television, and personal self-care.
AMD is the leading cause of vision loss for people aged 60 and older in the United States. According to the American Academy of Ophthalmology, 10-15 million individuals have AMD and about 10% of people who are affected have the “wet” type of AMD.
Wet (Neovascular) Macular Degeneration
In wet, or exudative, macular degeneration (AMD), the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal new blood vessels that develop into a cluster under the macula, called choroidal neovascularization (neo = new; vascular = blood vessels).
Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid under the macula, causing it to lift up and pull away from its base. This damages the fragile photoreceptor cells, which sense and receive light, resulting in a rapid and severe loss of central vision.
Dry Macular Degeneration
The dry (also called atrophic) type of AMD affects approximately 80-90% of individuals with AMD. Its cause is unknown, it tends to progress more slowly than the wet type, and there is not – as of yet – an approved treatment or cure.
“Atrophy” refers to the degeneration of cells in a portion of the body; in this case, the cell degeneration occurs in the retina.
In dry age-related macular degeneration, small white or yellowish deposits, called drusen, form on the retina, in the macula, causing it to deteriorate or degenerate over time.
Drusen are the hallmark of dry AMD. These small yellow deposits beneath the retina are a buildup of waste materials, composed of cholesterol, protein, and fats. Typically, when drusen first form, they do not cause vision loss. However, they are a risk factor for progressing to vision loss.
Risk Factors for Macular Degeneration
The primary risk factors for AMD include the following:
- Smoking: Current smokers have a 2-3 times higher risk for developing AMD than do people who never smoked. It’s best to avoid second-hand smoke as well.
- Sunlight: Ultraviolet (UV) light is not visible to the human eye, but can damage the lens and retina. Blue light waves that make the sky, or any object, appear blue, are visible to the human eye and can also damage the lens and retina. Avoid UV light and blue/violet light as much as possible by wearing sunglasses with an amber, brown, or orange tint that blocks both blue and UV light.
- Uncontrolled hypertension: The National Eye Institute (NEI) reports that persons with hypertension were 1.5 times more likely to develop wet macular degeneration than persons without hypertension. It’s important to keep your blood pressure controlled within normal limits.
- A diet high in packaged, processed food and low in fresh vegetables: NEI suggests that eating antioxidant-rich foods, such as fresh fruits and dark green leafy vegetables (kale, collard greens, and spinach) may delay the onset or reduce the severity of AMD. Eating at least one serving of fatty fish (salmon, tuna, or trout) per week may also delay the onset or reduce the severity of AMD.
- Race: According to NEI, Whites/Caucasians are more likely to have AMD than people of African descent.
- Family history: NEI reports that individuals with a parent or sibling with AMD have a 3-4 times higher risk of developing AMD.
You can read more about the full range of AMD risk factors at Risk Factors for Age-Related Macular Degeneration on the VisionAware website.
More about the Study from Experimental Eye Research
Edited and excerpted from the study Abstract and Introduction, with the full article available online:
Age-related Macular Degeneration (AMD) is a common, irreversible blinding condition that leads to the loss of central vision. AMD has a complex etiology with both genetic as well as environmental risks factors, and share many similarities with Alzheimer’s disease. Recent findings have contributed significantly to unravelling its genetic architecture that is yet to be matched by molecular insights [i.e., the basic structure of molecules].
Studies are made more challenging by observations that aged and AMD retinas accumulate the highly pathogenic [i.e., causing disease] Alzheimer’s-related amyloid beta group of peptides, for which there appears to be no clear genetic basis. Analyses of human donor and animal eyes have identified retinal amyloid beta aggregates [i.e., clusters] in retinal ganglion cells, the inner nuclear layer, photoreceptors, as well as the retinal pigment epithelium. Amyloid beta is also a major drusen constituent; found correlated with elevated drusen-load and age, with a propensity to aggregate in retinas of advanced AMD.
Despite this evidence, how such a potent driver of neurodegeneration might impair the neuro-retina remains incompletely understood, and studies into this important aspect of retinopathy remains limited. In order to address this we exploited R28 rat retinal cells which, due to its heterogeneous [i.e., dissimilar or diverse] nature, offers diverse neuro-retinal cell types in which to study the molecular pathology of amyloid beta.
For the first time, we reveal that retinal neurons rapidly internalized amyloid beta 1-42, the most cytotoxic [i.e., causing cell damage or death] and aggregate-prone [i.e., tending to form clusters] amongst the amyloid beta family.
To assess whether amyloid beta could realistically localize to living retinas to mediate such effects, we sub-retinally injected nanomolar levels [i.e., an extremely small concentration] of … amyloid beta 1-42 into wildtype mice.
Our novel findings describe how retinal neurons internalize amyloid beta to transiently impair MAP-2 in a hitherto unreported manner. Our insights suggest a molecular pathway by which this could occur in the senescent [i.e., aging] eye, leading to complex diseases such as AMD.