Glaucoma News: Researchers Convert Stem Cells into Retinal Ganglion Cells for Future Targeted Glaucoma Treatment

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Using stem cells derived from human skin cells, university researchers from Indiana and Connecticut have demonstrated the ability to turn stem cells into retinal ganglion cells (RGCs), which are the neurons that conduct visual information from the eye to the brain. Their research goal is ultimately to develop therapies that can prevent, slow down, or cure the degenerative processes that accompany glaucoma and other optic nerve injuries.

Please note: Although this stem cell research has produced interesting results thus far, it is in its very earliest stages and must be subjected to additional, longer-term, rigorous study and clinical trials, encompassing many more years of research.

The research, entitled Stepwise Differentiation of Retinal Ganglion Cells from Human Pluripotent Stem Cells Enables Analysis of Glaucomatous Neurodegeneration (explained below) was published in the March 21, 2016 Early View edition of Stem Cells. Stem Cells, a peer-reviewed monthly journal, provides a forum for the prompt publication of original investigative papers and reviews that cover all aspects of stem cells and stem cell research.

The authors are Sarah K. Ohlemacher, Akshayalakshmi Sridhar, Yucheng Xiao, Alexandra E. Hochstetler, Mansoor Sarfarazi, Theodore R. Cummins, and Jason S. Meyer, who represent the following institutions: Indiana University – Purdue University Indianapolis; Indiana University, Indianapolis; and the University of Connecticut Health Center.

Some Basic Stem Cell Terminology

Here is a brief explanation of some key terms that are used in many types of stem cell research:

  • Pluripotent: A stem cell that has the power to develop into any type of bodily cell or tissue ("pluri" = many; "potent" = having power)
  • Induced pluripotent stem cells (iPSCs): A type of pluripotent stem cell that can be generated or "reprogrammed" directly from adult cells. Induced pluripotent stem cells require viruses to reprogram the cells, which has the potential to cause cancerous tumors.
  • Embryonic stem cells (ESCs): Can form any cell type in the body. However, they are in limited supply, and – due to their origins – have ethical issues attached to their use.
  • Human pluripotent stem cells (hPSCs): The term includes both human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs)
  • Autologous: Involving one individual as both donor and recipient
  • Retinal ganglion cells (RGCs): Neurons, or nervous system cells. They are located near the inner surface of the retina and give rise to optic nerve fibers that transmit information from the retina to several regions in the brain.

About the Stem Cell Glaucoma Research

From Researchers use stem cells to identify cellular processes related to glaucoma, via EurekAlert:

Using stem cells derived from human skin cells, researchers … have successfully demonstrated the ability to turn stem cells into retinal ganglion cells (RGCs), the neurons that conduct visual information from the eye to the brain. Their goal is the development of therapies to prevent or cure glaucoma. In addition to glaucoma, this work has potential implications for treatment of optic nerve injuries of the types incurred by soldiers in combat or athletes in contact sports.

In the study … the investigators took skin cells biopsied from volunteers with [a genetically inherited form of glaucoma, which results in damage and loss of RGCs] and from volunteers without the disease and genetically reprogrammed them to become pluripotent stem cells, meaning they are able to differentiate into any cell type in the body.

The researchers then directed the stem cells to become RGCs, at which point the cells began adopting features specific to RGCs – features that were different in the cells of individuals with glaucoma than in the cells that came from healthy individuals.

"Skin cells from individuals with glaucoma are no different from skin cells of those without glaucoma," said [study author Jason S. Meyer], a cell biologist and stem cell researcher. "However, when we turned glaucoma patients' skin cells into stem cells and then into RGCs, the cells became unhealthy and started dying off at a much faster rate than those of healthy individuals.

"Now that we have produced cells that develop features of glaucoma in culture dishes, we want to see if compounds we add to these RGCs can slow down the degeneration process or prevent these cells from dying off. We already have found candidates that look promising and are studying them.

In the more distant future, we may be able to use healthy patient cells as substitute cells as we learn how to replace cells lost to the disease. It's a significant challenge, but it's the ultimate – and, we think, not unrealistic – long long-range goal."

What Is Glaucoma?

The term "glaucoma" describes a group of eye diseases that can lead to blindness by damaging the optic nerve. It is one of the leading causes of vision loss and blindness. The human eye continuously produces a fluid, called the aqueous, that must drain from the eye to maintain healthy eye pressure.

Types of Glaucoma

In primary open-angle glaucoma, the most common type of glaucoma, the eye's drainage canals become blocked, and the fluid accumulation causes pressure to build within the eye. This increasing pressure can cause damage to the optic nerve, which transmits information from the eye to the brain. Vision loss is usually gradual and often there are no early warning signs.

In angle-closure glaucoma, also called "acute" glaucoma, the aqueous cannot drain properly because the entrance to the drainage canal is either too narrow or is closed completely. In this case, eye pressure can rise very quickly and cause an acute glaucoma attack. Symptoms can include sudden eye pain, nausea, headaches, and blurred vision. Acute glaucoma is a true ocular emergency and requires immediate treatment.

In normal-tension glaucoma, also called low-tension/low pressure glaucoma, individuals with the disease experience optic nerve damage and subsequent vision loss, despite having normal intraocular [i.e., within the eye] pressure (IOP).

Most eye care professionals define the range of normal IOP as between 10 and 21 mm Hg [i.e., millimeters of mercury, which is a pressure measurement]. Most persons with glaucoma have an IOP measurement of greater than 21 mm Hg; persons with normal-tension glaucoma, however, have an IOP measurement within the normal range.

Visual Field Loss

Glaucoma results in peripheral (or side) vision loss initially, and the effect as this field loss progresses is like looking through a tube or into a narrow tunnel. This constricted "tunnel vision" effect makes it difficult to walk without bumping into objects that are off to the side, near the head, or at foot level.

A living room viewed through a constricted visual field

A living room viewed through a constricted visual field.
Source: Making Life More Livable. Used with permission.

Glaucoma is an especially dangerous eye condition because most people do not experience any symptoms or early warning signs at the onset. Glaucoma can be treated, but it is not curable. The damage to the optic nerve from glaucoma cannot be reversed.

More about the Study from Stem Cells

From the study summary and abstract:

Human pluripotent stem cells (hPSCs), including both embryonic and induced pluripotent stem cells, possess the unique ability to readily differentiate into any cell type of the body, including cells of the retina.

Although previous studies have demonstrated the ability to differentiate hPSCs to a retinal lineage, the ability to derive retinal ganglion cells (RGCs) from hPSCs has been complicated by the lack of specific markers with which to identify these cells from a pluripotent source.

In the current study, the definitive identification of hPSC-derived RGCs was accomplished by their directed, stepwise differentiation [i.e., a series of distinct stages, or step by step] through an enriched retinal progenitor intermediary, with resultant RGCs expressing a full complement of associated features and proper functional characteristics.

[Note: Progenitor cells are early descendants of stem cells that can differentiate to form one or more kinds of cells, but cannot divide and reproduce indefinitely. A progenitor cell is often more limited than a stem cell in the kinds of cells it can become.]

These results served as the basis for the establishment of induced pluripotent stem cells (iPSCs) from a patient with a genetically inherited form of glaucoma, which results in damage and loss of RGCs.

Patient-derived RGCs specifically exhibited a dramatic increase in apoptosis (cell death), similar to the targeted loss of RGCs in glaucoma, which was significantly rescued by the addition of candidate neuroprotective factors.

Thus, the current study serves to establish a method by which to definitively acquire and identify RGCs from hPSCs and demonstrates the ability of hPSCs to serve as an effective in vitro model of disease progression. Moreover, iPSC-derived RGCs can be utilized for future drug screening approaches to identify targets for the treatment of glaucoma and other optic neuropathies.

VisionAware will provide updates of this stem cell research as they become available.

More about Stem Cell Vision Research at VisionAware

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