Stem Cell Therapy for Macular Degeneration

Age-related macular degeneration (AMD) is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field (the macula) because of damage to the retina. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults (>50 years). Macular degeneration can make it difficult or impossible to read or recognize faces, although enough peripheral vision remains to allow other activities of daily life.

Picture of the fundus showing intermediate age-related macular degeneration.
Starting from the inside of the eye and going towards the back, the three main layers at the back of the eye are the retina, which contains the nerves; the choroid, which contains the blood supply; and the sclera, which is the white of the eye.

The macula is the central area of the retina, which provides the most detailed central vision.

In the dry (nonexudative) form, cellular debris called drusen accumulate between the retina and the choroid, and the retina can become detached.

In the wet (exudative) form, which is more severe, blood vessels grow up from the choroid behind the retina, and the retina can also become detached.

It can be treated with laser coagulation, and with medication that stops and sometimes reverses the growth of blood vessels. The is a substantial amount of animal model studies showing that stem cells can reverse and or stabilize the vascularization processes, in the retina.

Although some macular dystrophies affecting younger individuals are sometimes referred to as macular degeneration, the term generally refers to age-related macular degeneration (AMD or ARMD).

Age-related macular degeneration begins with characteristic yellow deposits (drusen) in the macula, between the retinal pigment epithelium and the underlying choroid. Most people with these early changes (referred to as age-related maculopathy) have good vision. People with drusen can go on to develop advanced AMD. The risk is considerably higher when the drusen are large and numerous and associated with disturbance in the pigmented cell layer under the macula. Recent research suggests that large and soft drusen are related to elevated cholesterol deposits and may respond to cholesterol-lowering agents.

Dry AMD:
Central geographic atrophy, the “dry” form of advanced AMD, results from atrophy to the retinal pigment epithelial layer below the retina, which causes vision loss through loss of photoreceptors (rods and cones) in the central part of the eye. No medical or surgical treatment is available for this condition, however vitamin supplements with high doses of antioxidants, lutein and zeaxanthin, have been suggested by the National Eye Institute and others to slow the progression of dry macular degeneration and, in some patients, improve visual acuity.

Macular degeneration by itself will not lead to total blindness. For that matter, only a very small number of people with visual impairment are totally blind. In almost all cases, some vision remains. Other complicating conditions may possibly lead to such an acute condition (severe stroke or trauma, untreated glaucoma, etc.), but few macular degeneration patients experience total visual loss.

The area of the macula comprises only about 2.1% of the retina, and the remaining 97.9% (the peripheral field) remains unaffected by the disease. Interestingly, even though the macula provides such a small fraction of the visual field, almost half of the visual cortex is devoted to processing macular information.

The loss of central vision profoundly affects visual functioning. It is not possible, for example, to read without central vision. Pictures that attempt to depict the central visual loss of macular degeneration with a black spot do not really do justice to the devastating nature of the visual loss. This can be demonstrated by printing letters 6 inches high on a piece of paper and attempting to identify them while looking straight ahead and holding the paper slightly to the side. Most people find this difficult to do.

There is a loss of contrast sensitivity, so that contours, shadows, and color vision are less vivid. The loss in contrast sensitivity can be quickly and easily measured by a contrast sensitivity test performed either at home or by an eye specialist.

The practical application of AMD-associated markers, such as seen above, is in the prediction of progression of AMD from early stages of the disease to neovascularization.

A family of immune mediators has been shown to be plentiful in drusen, the cellular debris associated with macular degeneration. Complement factor H (CFH) is an important inhibitor of this inflammatory cascade and a disease-associated polymorphism in the CFH gene strongly associates with AMD. Thus an AMD pathophysiological model of chronic low grade complement activation and inflammation in the macula has been advanced. Lending credibility to this has been the discovery of disease-associated genetic polymorphisms in other elements of the complement cascade including complement component 3 (C3).

The role of retinal oxidative stress in the etiology of AMD by causing further inflammation of the macula is suggested by the enhanced rate of disease in smokers and those exposed to UV irradiation. Mitochondria are a major source of oxygen free radicals that occur as a byproduct of energy metabolism. Mitochondrial gene polymorphisms, such as that in the MT-ND2 molecule, predicts wet AMD.

A powerful predictor of AMD is found on chromosome 10q26 at LOC 387715. An insertion/deletion polymorphism at this site reduces expression of the ARMS2 gene though destabilization of its mRNA through deletion of the polyadenylation signal. ARMS2 protein may localize to the mitochondria and participate in energy metabolism, though much remains to be discovered about its function.

Other gene markers of progression risk includes Tissue Inhibitor of Metalloproteinase 3 (TIMP3) suggesting a role for intracellular matrix metabolism in AMD progression. Variations in cholesterol metabolising genes such as the hepatic lipase (LIPC), cholesterol ester transferase (CETP), lipoprotein lipase (LPL) and the ABC-binding cassette A1 (ABCA1) correlate with disease progression, Early stigmata of disease, drusen, are rich in cholesterol, offering face validity to the results of genome wide association studies