STEM CELL THERAPY FOR AMD

Yulius Dirck Syamsuddin Siahaya

030.07.280

Abstract
Age-related Macular Degeneration (AMD) is the major cause of vision loss after age 50
in the United States.[4] Although an important association of the complement cascade with AMD
has recently been made, we still do not understand the pathogenesis of the disease. AMD is
characterized by loss of the retinal pigment epithelium (RPE) within the macula (i.e., the center
of the retina), and in turn, loss of the overlying foveal photoreceptors. Since RPE and
photoreceptors can both be generated from stem cells using cell culture, there is hope for future
cell replacement therapy. But, aging changes in Bruch's membrane, the scaffold on which the
RPE are anchored, may complicate such therapy, and require surgical repair of Bruch's
membrane to provide a suitable environment for cell survival and function. In this paper, well
see how the stem cell therapy can effectively cured the AMD.

CHAPTER I
Introduction
Age-related Macular Degeneration (AMD) is a retina disease which destroy a part or a
whole retina or retinal epithelial pigment. This disease caused by lipid product which precipitate
in the Bruch membrane, or it caused by an abnormalities of coroid blood vessel which make a
subretinal neovascular membrane.
Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss
in the industrialized world. Physicians have traditionally recognized two types of macular
degeneration: dry and wet. The dry, or nonexudative, form involves both atrophic and
hypertrophic changes of the retinal pigment epithelium (RPE) underlying the central macula, as
well as drusen deposition beneath the RPE. Patients with nonexudative AMD can progress to the
wet, or exudative, form of AMD, in which pathologic choroidal neovascular membranes
(CNVM) develop under the retina, leak fluid and blood, and, ultimately, cause a centrally
blinding disciform scar over a relatively short time course if left untreated. Approximately 1020% of patients with nonexudative AMD eventually progress to the exudative form, which is
responsible for the majority of the estimated 1.75 million cases of advanced AMD in the United
States.
The stem cell therapy is a new path to make the patient of AMD can see clearly, this
therapy can cure their scotoma and make their vision better. Just like before they had AMD.

CHAPTER II
I. Epidemiology
AMD is the leading cause of irreversible visual loss in the United States, with variable
degrees of age-related macular changes occurring in more than 10% of the population aged 65-74
years and 25% of the population older than 74 years

II. The Pathogenesis and pathophysiology of Age-related Macular Degeneration

AMD has two types of classification, the exudative (wet) AMD and the non-exudative
(dry) AMD. Each one of them had their own pathogenesis. The pathogenesis of the exudative
AMD is begin by the abnormalities of choroid vessel, this vessel grown through the Bruch
membrane and retinal epithelial pigment into the subretinal space where this abnormal vessel
make a subretinal neovaskular membrane. The symptom caused by the leak of fluid or blood of
the vessels, fill the subretinal space or even going to vitreous right through the retina. The
patogenesis of the non-exudative AMD is begin by the deposit of lipid in the Bruch membrane,
which caused by the failure of the excretion function from the retinal epithelial pigment. These
deposits can be seen using oftalmoscopy, this yellow plaque which caused by the deposit of lipid
is called drusen.[1]
Drusen are extracellular between the RPE and the bruch membrane. Usually small drusen
are considered normal in ageing process. In AMD drusen becomes large and diffuse. These
pathological drusen contains pyridinium bisretinoid A2E. Which has many multiple pathogenic
effects.[8] The pathologic drusen will make the RPE atrophy, which result in secondary loss of the
overlying photoreceptor cells that it supplies. And in the other hand, if the neovaskular membrane

ruptures, the blood will fill the subretinal membrane and even the retina itself. This event will
make the vision of the patient is blurred.[5,6]

Figure 1. Dry and Wet AMD

III. The Sign and Symptom of Age-related Macular degeneration

Patients with ARM are often asymptomatic or sometimes notice mild symptoms,
including minimally blurred central visual acuity, and contrast and color disturbances. If
geographic atrophy develops in the macular region, patients may notice a scotoma (blind spot),
which can slowly enlarge over months to years before eventually stabilizing. The patient might
also notice about a distortion of vision (metamorfopsia).[1,5,6]

Figure 2. Normal vision and vision in AMD

IV. The Usual Therapy for Age-related Macular Degeneration

There is no therapy for curing non-exudative AMD, the therapy is just to help their
visions better, using tools such like telescope. The education to the patient must clear, so even
they lost of the central vision, they wont lose the peripheral vision. So they wont have to worry
about total blindness. Meanwhile, at the patient which had an exudative AMD which on the
angiogram fluorescent shows the choroidal neovascular membranes is excentric to fovea, can be
obliterate with argon laser therapy. But sadly, these conditions can be happened again to the
patient.[1].
The other kind of therapy is using broad spectrum steroids to suppress the inflammation
event that occur in AMD. The target molecular therapy can be used on the wet AMD, which will
inhibits the growth of choroidal neovascularization[7]

V. Stem Cells
Stem cells have the remarkable potential to develop into many different cell types in the
body during early life and growth. In addition, in many tissues they serve as a sort of internal
repair system, dividing essentially without limit to replenish other cells as long as the person or

animal is still alive. When a stem cell divides, each new cell has the potential either to remain a
stem cell or become another type of cell with a more specialized function, such as a muscle cell, a
red blood cell, or a brain cell. Stem cells are distinguished from other cell types by two important
characteristics.[9]
First, they are unspecialized cells capable of renewing themselves through cell division,
sometimes after long periods of inactivity. Second, under certain physiologic or experimental
conditions, they can be induced to become tissue- or organ-specific cells with special functions.
In some organs, such as the gut and bone marrow, stem cells regularly divide to repair and
replace worn out or damaged tissues. In other organs, however, such as the pancreas and the
heart, stem cells only divide under special conditions. Until recently, scientists primarily worked
with two kinds of stem cells from animals and humans embryonic stem cells and non-embryonic.
[9]

VI. Stem Cells Therapy as Part of a Multi-step Approach in AMD

Currently, there is significant interest in using stem cells to treat AMD. This includes the
use of retinal progenitors from the eye as well as embryonic stem cells and induced pluripotent
stem cells, which can be generated by re-expression of embryonic stem cell specification genes in
skin fibroblasts. Such cells can in theory be used to replace both RPE and photoreceptors in
AMD patients. And studies in culture demonstrate that these stem cells can give rise to RPE and
multiple retinal lineages, and preliminary studies in mice provide hope for functional integration
of such cells. The test in mice is showing a great result.[4]
The scientist had already tried a multi-step approach as Maculoplasty. Successful
Maculoplasty may then include reconstruction or replacement of Bruchs membrane within the

macula (to restore the integrity of the substrate for proper RPE cell attachment),
immunosuppression if allogeneic cells are to be transplanted, and finally cell replacement using
RPE and photoreceptor progenitors derived from stem cells in culture. So the stem cell makes a
new RPE, and the scar tissue on the RPE is removed by maculoplasty. [4]
The first trials of cell replacement have been performed using mature photoreceptors or
their late progenitors as donor cells for transplantation into dystrophic mouse retinas. They have
been shown to partially engraft and to survive for long periods in the host retina, but they fail to
integrate efficiently within the host tissue.1 Alternative cell sources such as neural
progenitor/stem cells have therefore been investigated.[2]

VII. The Surgical Report

Bone Marrow Collection
On the first day, bone marrow is collected from the patient's iliac crest (hip bone) using
thin-needle mini-puncture under local anesthesia. The entire procedure normally takes about 30
minutes. Once the bone marrow collection is complete, patients may return to their hotel and go
about normal activities. Patients who receive general anesthesia must lie down for a short
recovery period before returning to their hotel.[3]
Laboratory Processing
The next day, the stem cells are processed from the bone marrow in a state-of-the-art,
government approved (cGMP) laboratory. In the lab, both the quantity and quality of the stem
cells are measured. These cells have the potential to transform into multiple types of cells and are
capable of regenerating or repairing damaged tissue.[3]

Stem Cell Implantation

On the third day, the stem cells are implanted back into the patient via retrobulbar
injection by an experienced ophthalmologist. Retrobulbar means "behind the eye" and therefore
the stem cells are implanted into the space behind the eye ball by inserting a small needle under
the bottom of the eye. The needle is then guided into the retrobulbar space. Once the needle is in
the correct position, the stem cells are injected. Retrobulbar injection can be performed under
local or general anesthesia.[3]
Surgical Result
The results are, two weeks after the treatment, during an objective, standardized
examination, this patient showed significant improvement. The next picture shows the Threshold
Fovea

Map.

Clearly

visible

is

the

improvement

in

retinal

sensitivity.

The following picture shows the Visual Fields. Here, too, one can see an improved retinal
sensitivity.[3]

Figure 3. Visual Field before and after treatment

Figure 4. Retinal sensitivity before and after treatment

CHAPTER IV
Conclusion
AMD had great numbers in USA, and many other industrial countries. The impact of this
disease is so great, it can make an old people to lose their centar vision, they had blind spot on
their vision and many others. But there is a new therapy for this disease, it called stem cells
therapy. About the stem cell therapy the result of the pre-clinical tiran and the clinical trial of this
therapy showing good signs. So the people with AMD can cure their sickness and they can see
things clearly now.

References
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James B, Chew C, Bron A. Lecture Notes Oftalmology. 9 thed. Jakarta : Penerbit
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2003; 87: 1058-1059.
3.
The X-cell center at the institute of regenerative medicine. Stem cell treatment for
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4.
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Available
at
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http://emedicine.medscape.com/article/1226030-overview. Accesed May 30, 2010.
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Ambati J, Ambati JK, et al. Age-Related Macular Degeneration: Etiology, Pathogenesis,
and Therapeutic Strategies. Survey of Opthalmology 2003; 48:257-293.
8.
Mathieu JM, Schloendorn J, et al. Medical Bioremediation of Age-Related
Disease.Microbial Cell Factories 2009; 8: 8-9.
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http://stemcells.nih.gov/info/basics/basics1.asp. Accessed: June 6, 2010.