Stem cell therapy for macular degeneration is an emerging treatment approach aimed at restoring vision in individuals suffering from various forms of macular degeneration, particularly age-related macular degeneration (AMD). [1] This therapy involves the transplantation of stem cells into the retina to replace damaged or lost retinal pigment epithelium (RPE) and photoreceptor cells, which are critical for central vision. Clinical trials have shown promise in stabilizing or improving visual function, but are nevertheless inefficient. [2]
The first fetal retinal transplant into the anterior chamber of animal eyes was reported in 1959. In 1980, experiments involving cell cultures of retinal pigment epithelium (RPE) began. Human RPE cells grown in culture were subsequently transplanted into animal eyes, initially using open techniques and later through closed cavity vitrectomy methods. [1]
In 1991, Gholam Peyman attempted to transplant RPE in humans, but the success rate was limited. Later efforts focused on allogenic fetal RPE cell transplantation, which faced significant challenges due to immune rejection. It was observed that rejection rates were lower in cases of dry age-related macular degeneration (AMD) compared to the wet form of the disease. Autologous RPE transplantation became more common, using two main techniques: RPE suspension and full-thickness RPE-choroid transplantation. Clinical outcomes from autologous RPE-choroid transplantation, where tissue from the eye’s periphery is transplanted to a diseased area, have shown promise. [3]
Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. Sheets of retinal cells used in these procedures were initially harvested from aborted fetuses, which raised ethical concerns for some. These retinal sheets, when transplanted over damaged corneas, stimulated repair and eventually restored vision. [4] [5] In June 2005, a team led by Sheraz Daya at Queen Victoria Hospital in Sussex, England, restored sight in forty patients using a similar technique with adult stem cells sourced from the patient, a relative, or a cadaver. [6]
In 2014, surgeons at Riken Institute’s Center for Developmental Biology reported the first transplantation of induced pluripotent stem cells (iPSCs) into a human patient. This clinical study involved creating a retinal sheet from iPSCs, developed by Shinya Yamanaka, which were reprogrammed from the patient's own mature cells. The retinal sheet was transplanted into a woman in her 70s suffering from age-related macular degeneration (AMD), a condition that blurs central vision and can lead to blindness. The use of iPSCs aimed to halt the progression of AMD. In March 2017, the team conducted the first successful transplant of retinal cells created from donor-derived iPSCs into a patient with advanced wet AMD. This surgery was made more efficient by using "super donor" cells, derived from individuals with specific white blood cell types that reduce the risk of immune rejection. Approximately 250,000 retinal pigment epithelial cells, generated from these donor-derived iPSCs, were transplanted into the patient’s eye. [7]
The retina is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then processes that image within the retina and sends nerve impulses along the optic nerve to the visual cortex to create visual perception. The retina serves a function which is in many ways analogous to that of the film or image sensor in a camera.
Retinitis pigmentosa (RP) is a member of a group of genetic disorders called Inherited Retinal Dystrophy (IRD) that cause loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision. As peripheral vision worsens, people may experience "tunnel vision". Complete blindness is uncommon. Onset of symptoms is generally gradual and often begins in childhood.
Macular degeneration, also known as age-related macular degeneration, is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, some people experience a gradual worsening of vision that may affect one or both eyes. While it does not result in complete blindness, loss of central vision can make it hard to recognize faces, drive, read, or perform other activities of daily life. Visual hallucinations may also occur.
A cone dystrophy is an inherited ocular disorder characterized by the loss of cone cells, the photoreceptors responsible for both central and color vision.
A retinal implant is a visual prosthesis for restoration of sight to patients blinded by retinal degeneration. The system is meant to partially restore useful vision to those who have lost their photoreceptors due to retinal diseases such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Retinal implants are being developed by a number of private companies and research institutions, and three types are in clinical trials: epiretinal, subretinal, and suprachoroidal. The implants introduce visual information into the retina by electrically stimulating the surviving retinal neurons. So far, elicited percepts had rather low resolution, and may be suitable for light perception and recognition of simple objects.
Choroideremia is a rare, X-linked recessive form of hereditary retinal degeneration that affects roughly 1 in 50,000 males. The disease causes a gradual loss of vision, starting with childhood night blindness, followed by peripheral vision loss and progressing to loss of central vision later in life. Progression continues throughout the individual's life, but both the rate of change and the degree of visual loss are variable among those affected, even within the same family.
Drusen, from the German word for node or geode, are tiny yellow or white accumulations of extracellular material that build up between Bruch's membrane and the retinal pigment epithelium of the eye. The presence of a few small ("hard") drusen is normal with advancing age, and most people over 40 have some hard drusen. However, the presence of larger and more numerous drusen in the macula is a common early sign of age-related macular degeneration (AMD).
The pigmented layer of retina or retinal pigment epithelium (RPE) is the pigmented cell layer just outside the neurosensory retina that nourishes retinal visual cells, and is firmly attached to the underlying choroid and overlying retinal visual cells.
Stargardt disease is the most common inherited single-gene retinal disease. In terms of the first description of the disease, it follows an autosomal recessive inheritance pattern, which has been later linked to bi-allelic ABCA4 gene variants (STGD1). However, there are Stargardt-like diseases with mimicking phenotypes that are referred to as STGD3 and STGD4, and have a autosomal dominant inheritance due to defects with ELOVL4 or PROM1 genes, respectively. It is characterized by macular degeneration that begins in childhood, adolescence or adulthood, resulting in progressive loss of vision.
Epiretinal membrane or macular pucker is a disease of the eye in response to changes in the vitreous humor or more rarely, diabetes. Sometimes, as a result of immune system response to protect the retina, cells converge in the macular area as the vitreous ages and pulls away in posterior vitreous detachment (PVD).
Intraocular hemorrhage is bleeding inside the eye. Bleeding can occur from any structure of the eye where there is vasculature or blood flow, including the anterior chamber, vitreous cavity, retina, choroid, suprachoroidal space, or optic disc.
Macular telangiectasia is a condition of the retina, the light-sensing tissue at the back of the eye that causes gradual deterioration of central vision, interfering with tasks such as reading and driving.
Retinal gene therapy holds a promise in treating different forms of non-inherited and inherited blindness.
Lineage Cell Therapeutics, Inc. is a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs. Lineage’s programs are based on its robust proprietary cell-based therapy platform and associated in-house development and manufacturing capabilities. With this platform Lineage develops and manufactures specialized, terminally differentiated human cells from its pluripotent and progenitor cell starting materials. These differentiated cells are developed to either replace or support cells that are dysfunctional or absent due to degenerative disease or traumatic injury or administered as a means of helping the body mount an effective immune response to cancer.
Emixustat is a small molecule notable for its establishment of a new class of compounds known as visual cycle modulators (VCMs). Formulated as the hydrochloride salt, emixustat hydrochloride, it is the first synthetic medicinal compound shown to affect retinal disease processes when taken by mouth. Emixustat was invented by the British-American chemist, Ian L. Scott, and is currently in Phase 3 trials for dry, age-related macular degeneration (AMD).
Robert E. MacLaren FMedSci FRCOphth FRCS FACS VR is a British ophthalmologist who has led pioneering work in the treatment of blindness caused by diseases of the retina. He is Professor of Ophthalmology at the University of Oxford and Honorary Professor of Ophthalmology at the UCL Institute of Ophthalmology. He is a Consultant Ophthalmologist at the Oxford Eye Hospital. He is also an Honorary Consultant Vitreo-retinal Surgeon at the Moorfields Eye Hospital. MacLaren is an NIHR Senior Investigator, or lead researcher, for the speciality of Ophthalmology. In addition, he is a member of the research committee of Euretina: the European Society of Retina specialists, Fellow of Merton College, in Oxford and a Fellow of the Higher Education Academy.
Geographic atrophy (GA), also known as atrophic age-related macular degeneration (AMD) or advanced dry AMD, is an advanced form of age-related macular degeneration that can result in the progressive and irreversible loss of retinal tissue (photoreceptors, retinal pigment epithelium, choriocapillaris) which can lead to a loss of visual function over time. It is estimated that GA affects over 5 million people worldwide and approximately 1 million patients in the US, which is similar to the prevalence of neovascular (wet) AMD, the other advanced form of the disease.
Masayo Takahashi is a Japanese medical physician, ophthalmologist and stem cell researcher.
Pachychoroid disorders of the macula represent a group of diseases affecting the central part of the retina of the eye, the macula. Due to thickening and congestion of the highly vascularized layer underneath the macula, the choroid, damage to the retinal pigment epithelium and the retinal photoreceptor cells ensues. This leads to impaired vision. The best known representative of the pachychoroid disease spectrum, central serous chorioretinopathy, is the fourth most common cause of irreversible damage to the macula:.
Ruth Ashery-Padan is an Israeli geneticist who is a professor and principal investigator in the Department of Human Genetics and Molecular Medicine at the Sackler Faculty of Medicine, Tel Aviv University. She is known for her contributions to the understanding of ocular development.