Rao, Gullapalli N.

Sangwan, Virender S.

Vemuganti, Geeta K.

English

Publications of the IAS Fellows

Clinical and Experimental Optometry 90.5 September 2007© 2007 The Authors
Journal compilation © 2007 Optometrists Association Australia 315
C L I N I C A L  A N D  E X P E R I M E N T A L
OPTOMETRY
Clin Exp Optom 2007; 90: 5: 315–316 DOI:10.1111/j.1444-0938.2007.00156.x
Geeta K Vemuganti*† MD
Virender S Sangwan*#§ MS
Gullapalli N Rao# MD
* Ophthalmic Pathology Service
† Sudhakar and Sreekant Ravi Stem Cell 
Laboratory, Professor Brien Holden Eye 
Research Centre, Hyderabad Eye 
Research Foundation
# Cornea and Anterior Segment Service
§ Uveitis Service, LV Prasad Eye Institute, 
Hyderabad, India
E-mail: gnrao@lvpei.org
Stem cell biology is a fast-emerging field
that offers promise of cell-based tools for
the treatment of a wide range of recalci-
trant diseases that are not amenable to
other forms of therapy. By definition, stem
cells are cells with a capacity for unlimited
or prolonged self-renewal and can pro-
duce at least one type of differentiated cell
associated with the tissue.1 The term ‘cell
therapy’ is not limited to application of
stem cells alone but encompasses a large
gamut of rapidly developing scientific
disciplines, including stem cell biology,
immunology, tissue engineering, molecu-
lar biology, biomaterials, transplantation
biology, regenerative medicine and clini-
cal research. Blood transfusions and
bone marrow transplantation are prime
examples of the successful application of
cell-based  therapies.  Recent  advances
in cellular and molecular biology have
expanded the potential applications of
this approach to other medical fields like
ophthalmology, cardiology, neurology,
dermatology, dentistry and orthopaedics.
Another recent concept that is chal-
lenged by the developmental biologists is
the phenomenon of ‘plasticity’ in adult
stem cells, which has immense clinical
potential in cell replacement therapy and
regenerative medicine.2 The classic exam-
ple of such adult cells is the bone marrow
mesenchymal stem cell, which besides dif-
ferentiation into bone, cartilage, smooth
muscle and skeletal muscle, has also been
reported to trans-differentiate into skin,
liver and brain cells (neurons and glia).3–5
In cardiology, cell therapy was intro-
duced to improve the remodelling follow-
ing myocardial infarction using bone
marrow-derived stem cells and skeletal
myoblasts with varying success.6 Different
mechanisms have been proposed to
explain the beneficial effects of cell-
based therapy, which include cell trans-
differentiation, cell fusion and release of
paracrine growth factors or probably
multiple mechanisms. Similarly, efforts
are being made to search for alternative
sources of cell therapy for diabetes melli-
tus, stroke, spinal cord injuries and other
diseases. Preclinical experimental studies
have included the application of human
stem cells from various sources including
the brain, bone marrow, umbilical cord
and adipose tissue.
STEM CELL THERAPY FOR THE EYE
In ophthalmology, reconstruction of the
ocular surface in patients suffering from
intractable blinding ocular surface disease
has become possible with the advent of
techniques of ex vivo expansion and trans-
plantation of limbal epithelial stem cells
onto the cornea.7–9 Different groups have
used different techniques and substrates to
cultivate the limbal cells with almost similar
clinical outcomes of about 50 to 70 per cent
success at the end of three to five years.
The advantages of the technique devel-
oped by the group in India9 include use of
denuded human amniotic membrane,
feeder cell free method, use of autologous
serum, submerged technique of culturing
and use of cultured monolayered epithe-
lium generated within 10 to 12 days of
cultivation. This cost-effective technique
could be translated into an extended clin-
ical trial of treating 450 patients at tertiary
eye-care centres in a developing country
like India. The patients who underwent
subsequent corneal transplantation for
visual rehabilitation provided a unique
opportunity for documenting the in vivo
survival and stratification of transplanted
cells, thus fulfilling the most important cri-
teria of successful cell therapy that can
rarely be documented in other systems.
This system provides proof of integration
and functional restoration after cell ther-
apy, without causing any harm to the recip-
ient. Although the clinical outcome of this
new technique is well established,10,11 there
are still many unanswered questions.
These include rigorous characterisation of
limbal stem cells, the mechanism and fac-
tors influencing the homing of stem cells
from transplanted epithelium to limbal
niche, and the long-term survival of trans-
planted cells.
The promise of stem cell therapy for eye disorders
GUEST EDITORIAL
Guest editorial Vemuganti, Sangwan and Rao
Clinical and Experimental Optometry 90.5 September 2007
316
© 2007 The Authors
Journal compilation © 2007 Optometrists Association Australia
Another challenge in eye disease is the
treatment for irreversible photoreceptor
loss in many retinal conditions. Repair of
such damage by cell transplantation is one
of the most feasible types of central ner-
vous system repair; photoreceptor degen-
eration initially leaves the inner retinal
circuitry intact and new photoreceptors
need to make only single, short synaptic
connections to contribute to the retino-
topic map. So far, brain- and retina-
derived stem cells from foetal and adult
tissues transplanted into adult retina have
shown little evidence of being able to inte-
grate into the outer nuclear layer and dif-
ferentiate into new photoreceptors.
Approaches to treating this disease
include:
1. replacing the defective gene
2. introducing a drug or agent that either
retards or arrests the premature cell
death in the photoreceptors
3. introducing electronic chips
4. replacing the damaged cells by cellular
therapy.
Gene therapy is aimed at counteracting
the defective gene by substituting it with
the normal gene material at the target
site. Though successful visual recovery
has been reported with gene therapy in
canine models,12 challenges remain in
identifying a safe and reliable vector for
clinical application and its long-term suc-
cess. Introduction of trophic or survival
factors into the eye, directly or through
implants, is another novel way of retarding
the premature cell death. The challenge
lies in delivering the drug to the appropri-
ate site in a safe and a sustained manner.
Electronic chips, similar to those used for
audio aids, have shown exciting results but
the technology is still in its infancy.
These developments permit us to think
optimistically of growing retinal tissue
using appropriate cells, conditions and
engineering techniques, which, if they
clear the scientific and ethical hurdles,
would pave the way for clinical application
in the near future. We would need to iden-
tify the stem cells that would replace the
photoreceptor and other cells of the
retina, multiply/grow them in sufficient
quantities, organise them into functional
units, introduce them at the site in an
appropriate way, allow them to survive and
integrate into the host, so that ultimately,
they function appropriately in a safe man-
ner. The following cells have been pro-
posed to have the proliferative potential
to regenerate neuronal cells and photore-
ceptors: embryonic stem cells, retinal
progenitor cells from foetal or post-natal
retina, progenitor cells from the iris and
ciliary body and bone marrow stromal
cells.13–15
In summary, the advances made in the
field of stem cell biology have contributed
immensely to the field of ophthalmology,
which has now taken a lead role in trans-
lational research. Whenever available, use
of autologous tissues with minimal and no
expansion is one of logical choice for cell
therapy, thus obviating the ethical hurdles
that are raised with the use of embryonic
or foetal stem cells. The eye is one of the
perfect organs where cell therapy can be
monitored and hence, it comes as no sur-
prise that it would be considered as a per-
fect model for providing proof of concept
of such novel forms of cell therapy.
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The promise of stem cell therapy for eye disorders

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The promise of stem cell therapy for eye disorders

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