Using Stem Cells to Treat Macular Degeneration

By Jawad Braick

Macular degeneration is progressive loss of vision to the point of legal blindness due to damage to the macula, the part of the eye responsible for detailed, sharp vision.

The macula contains photoreceptor cells, which take in light, and retinal pigmented epithelium (RPE) cells, which nourish the photoreceptors cells.

Macular degeneration begins to occur when RPE cells die and are unable to nourish the photoreceptors and in turn, they die and light isn’t taken in at that area of the eye.

Macular degeneration characterized by progressive loss of fine acuity vision in the central portion of the visual.

What is macular degeneration?

Macular degeneration comes in two forms: age-related macular degeneration, AMD, and stargardt’s disease.

AMD is as a result of dyeing photoreceptor and RPE cells that occur because of the natural aging process.

Stargardt’s disease is caused by dyeing photoreceptor and RPE cells due to a genetic mutation. There are two forms of stargardt’s disease.

Forms of macular degeneration

The most common form of stargardt’s disease is the recessive form caused by a mutation in ABCA4 gene.

The ABCA4 gene is located on the short arm of chromosome 1 in position 22

More than 500 mutations in this gene have been known to cause macular degeneration, most of which change single amino acids

Stargardts Disease

The damage to photoreceptor cells is caused by the build up of toxic substances in the cell

When light enters the retina and is converted to electrical signals, phototransduction a substance called N-retinyl-phosphatidyletholamine (NR-PE) is produced as bi-product. A protein called flippase is supposed to bring NR-PE out of the cell but if this protein is malfunctioning NR-PE builds up in the cell

NR-PE then combines with another molecule to produce lipofuscin, a toxic substance which causes damage to the cells and they will eventually die.

Stargardt’s Disease

The rarer form of Stargardt’s Disease is the dominant form caused by a mutation in the EVOVL4 gene

The EVOVL4 gene is located on the long arm of chromosome 6 in position 14. At least 3 mutations in this gene have been known to cause macular degeneration.

Stargardts Disease

Death of the photoreceptor and RPE cells can also be caused by interference with cell functions.

The EVOVL4 gene codes for the protein elongase. Its job is to assist in the formation of very long-chain fatty acids by adding carbon molecules.

A mutated EVOVL4 gene sends premature signals in the instructions to make elongase. As a result, the protein is unable to stay in endoplasmic reticulum and clumps together (aggregates). These aggregates can not make very long-chain fatty acids can interfere with other cell functions and cause cell death.

Stargardt’s Disease

A stem cell is a self renewing cell capable of differentiating into a specialized cell

Pluripotent stem cells-stem cells that can differentiate into most cell types Multipotent stem cells- stem cells that differentiate into a few cell types Induced Pluripotent stem cells (iPS)-specialized cells that were reverted back

to pluripotent stem cells Embryonic stem cells-pluripotent stem cells from an embryo Adult stem cells- multipotent stem cells from various areas of an adult body

Stem Cells

The eye is one of the few areas of the body that is immune privileged. This means that the immune system isn’t very active, in the eye.

Immune privilege is characterized by the ability to tolerate antigens without eliciting an inflammatory immune response.

Some mechanisms that maintain immune privilege in the eye are physical barriers, the inhibitory ocular environment, and the ability to regulate systemic immune responses.

The Eye is Immune Privileged

Immune privilege allows stem cells to work to their full potential.

Usually implanted stem cells are rejected by the body and are recognized as antigens by the immune system, whether they are from a donor or the patient themselves. As a result, immune system attacks and destroys the stem cells.

Why immune privilege is good?

Scientists hope to inject embryonic stem cells into the macula then the stem cells would differentiate into RPE

Also scientists, want to inject embryonic stem cell-derived RPE cells into the macula rather have them differentiate after being injected

Possible Treatment Methods

Two phase 1 trials were conducted in which two patients were injected were embryonic stem cell-derived RPE cells into one eye. One had AMD and the other had Stargardt’s Disease

Both patients tolerated the treatment well and said they had improved vision in the treated eye

Current Tests

The inserted stem cells could proliferate and form a tumor

Even though the eye is immune privileged the immune system could still attack and destroy the stem cells

The cells may not integrate and function due to damage in tissue

Potential Problems