Could the Loss of an Anti-Aging Gene Contribute to Wet and Dry Macular Degeneration?

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Photograph of a retina with wet age-related macular degeneration

A team of researchers has determined that the loss of a particular anti-aging, or aging-suppressor, gene – known as Klotho protein (KL) – induces retinal deterioration in mice and may contribute to both wet and dry age-related macular degeneration (AMD). The KL gene helps to protect against oxidative stress, which causes dry AMD, and inhibits harmful blood vessel growth in the eye, which is the primary cause of wet AMD. (Please note that this research is in its earliest stages and has been conducted only with laboratory mice.)

The research, entitled Klotho Regulates Retinal Pigment Epithelial Functions and Protects Against Oxidative Stress (explained below), was published in the October 9, 2013 issue of The Journal of Neuroscience, the official journal of the Society for Neuroscience.

The authors are Maria Kokkinaki, Mones Abu-Asab, Nishantha Gunawardena, Gerard Ahern, Monica Javidnia, John Young, and Nady Golestaneh, who represent the following institutions: Georgetown University Medical Center, Washington, DC; Howard University College of Medicine, Washington, DC; and the National Eye Institute, National Institutes of Health.

About Wet Macular Degeneration and Blood Vessel Growth

In wet macular degeneration, the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal blood vessels that develop into a cluster under the macula (called choroidal neovascularization).

The macula is the part of the retina that provides the clearest central vision. 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.

Angiogenesis is a term used to describe the growth of new blood vessels and plays a crucial role in the normal development of body organs and tissue. Sometimes, however, excessive and abnormal blood vessel development can occur in diseases such as cancer (tumor growth), rheumatoid arthritis, and age-related macular degeneration (AMD).

Substances that stop the growth of these excessive blood vessels are called anti-angiogenic (anti=against; angio=vessel; genic=development), and anti-neovascular (anti=against; neo=new; vascular=blood vessels).

The focus of current anti-angiogenic treatments for wet AMD is to reduce the level of a particular protein (vascular endothelial growth factor, or VEGF) that stimulates abnormal blood vessel growth in the retina and macula.

About 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; however, there are clinical trials underway.

In dry age-related macular degeneration, small white or yellowish deposits, called drusen, form on the retina, in the macula – the small sensitive area in the center of the retina that provides clear central vision – causing it to deteriorate or degenerate over time.

Photograph of a retina with drusen

A retina with drusen

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.

More about the Research

From Loss of Anti-Aging Gene Possible Culprit in Age-Related Macular Degeneration in Science Daily:

Klotho, a hormone that is synthesized and secreted by some organs and tissues, is being studied worldwide for its anti-aging properties.

"We found four important functions Klotho provides in the human retina, which leads us to believe that the gene is crucial to the health of this light-sensitive tissue," says the study's senior investigator, Nady Golestaneh, PhD.

[Researchers] found that Klotho increases the activity of genes that synthesize the light-absorbing visual pigments in the retinal cells. Klotho also increases the expression of genes that protect against the oxidative stress known to damage the retina, and which can lead to dry macular degeneration. Klotho inhibits the vascular endothelial growth factor and therefore, might play an important role in inhibiting the overgrowth of blood vessels in the eye, a major cause of wet macular degeneration.

"For these reasons, we believe Klotho might be an interesting therapeutic target for age-related macular degeneration," Golestaneh says. "Gene therapy or cell therapy might be able to induce new expression of Klotho in the aging retina."

But she adds that before these strategies can be tested, research that quantifies the decline of Klotho expression in human eyes, and directly links this dysfunction to macular degeneration, must be undertaken.

Conclusions from the Research

From the study abstract:

The retinal pigment epithelium (RPE) is a highly specialized central nervous system tissue that plays crucial roles in [maintaining the equilibrium of retinal processes]. Age-related … changes in the RPE have been associated with retinal degenerative disorders; our understanding of the underlying molecular mechanisms, however, remains incomplete.

…our results demonstrate a critical function for Klotho protein (KL) in mouse retinal health in vivo, and a protective role toward human RPE cells in vitro. We conclude that KL is an important regulator of RPE [equilibrium], and propose that an age-dependent decline of KL expression may contribute to RPE degeneration and retinal pathology.

VisionAware will continue to provide updates on this macular degeneration research as they become available.


Topics:
Low Vision
Medical Updates
Macular Degeneration
Aging
Gene Therapy

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