scholarly journals Advancing a Stem Cell Therapy for Age-Related Macular Degeneration

2020 ◽  
Vol 15 (2) ◽  
pp. 89-97 ◽  
Author(s):  
Helen C. O’Neill ◽  
Ioannis J. Limnios ◽  
Nigel L. Barnett

The retinal pigment epithelium (RPE) is a multifunctional monolayer located at the back of the eye required for the survival and function of the light-sensing photoreceptors. In Age-related Macular Degeneration (AMD), the loss of RPE cells leads to photoreceptor death and permanent blindness. RPE cell transplantation aims to halt or reverse vision loss by preventing the death of photoreceptor cells and is considered one of the most viable applications of stem cell therapy in the field of regenerative medicine. Proof-of-concept of RPE cell transplantation for treating retinal degenerative disease, such as AMD, has long been established in animal models and humans using primary RPE cells, while recent research has focused on the transplantation of RPE cells derived from human pluripotent stem cells (hPSC). Early results from clinical trials indicate that transplantation of hPSC-derived RPE cells is safe and can improve vision in AMD patients. Current hPSC-RPE cell production protocols used in clinical trials are nevertheless inefficient. Treatment of large numbers of AMD patients using stem cellderived products may be dependent on the ability to generate functional cells from multiple hPSC lines using robust and clinically-compliant methods. Transplantation outcomes may be improved by delivering RPE cells on a thin porous membrane for better integration into the retina, and by manipulation of the outcome through control of immune rejection and inflammatory responses.

2015 ◽  
Vol 3 (1) ◽  
pp. 16-25
Author(s):  
Lisa C. Olmos ◽  
Hossein Nazari ◽  
Damien C. Rodger ◽  
Mark S. Humayun

2021 ◽  
Vol 10 (8) ◽  
pp. 1785
Author(s):  
Tadao Maeda ◽  
Sunao Sugita ◽  
Yasuo Kurimoto ◽  
Masayo Takahashi

Age-related macular degeneration (AMD) is a highly prevalent irreversible impairment in the elderly population worldwide. Stem cell therapies have been considered potentially viable for treating AMD through the direct replacement of degenerated cells or secretion of trophic factors that facilitate the survival of existing cells. Among them, the safety of pluripotent stem cell-derived retinal pigment epithelial (RPE) cell transplantation against AMD, and some hereditary retinal degenerative diseases, has been discussed to a certain extent in clinical studies of RPE cell transplantation. Preparations are in progress for its clinical application. On the other hand, clinical trials using somatic stem cells are also being conducted, though these had controversial outcomes. Retinal regenerative medicine using stem cells is expected to make steady progress toward practical use while new technologies are incorporated from various fields, thereby making the role of ophthalmologists in this field increasingly important.


2018 ◽  
Vol 5 (1) ◽  
pp. 31-46 ◽  
Author(s):  
Biswa P. Chatterji ◽  
Godiwala Mehvash ◽  
Sunder Roma

Background:According to WHO, 285 million people are visually impaired out of which, 39 million are classified as blind and the remaining 246 million people have low vision which comprises of moderate vision impairment and severe vision impairment. Therapies to treat major disorders leading to visual impairment like Age-related Macular Degeneration (AMD), Stargardt’s Disease (STGD), Retinitis Pigmentosa (RP) and corneal scarring are required.In the last decade, many advances have been made to treat these disorders using stem cell therapy. For corneal damage by accidental burns, scarring or limbal stem cell deficiencies which can lead to partial or total blindness, are treated with a risky intervention like keratoplasty. To overcome issues like graft rejection caused by keratoplasty as well as have a better outcome, limbal stem cell therapy has been introduced. Similarly, Retinal Pigment Epithelium (RPE) is a supporting tissue essential in nutrient transport, production of growth factors, phagocytosis of the photoreceptors and retinol cycling.Discussion and Conlusion:Degeneration of this monolayer causes many diseases that have no prevailing treatment; however, research is being carried out to replace this simple epithelial monolayer primarily with an autologous source of cells and currently using stem cells. This review discusses the advances made in the field of ocular stem cell therapy with regards to development, cultivation and novel methods used to deliver these cells to replace the corneal and retinal epithelium as a new standard for treatment.


2010 ◽  
Vol 04 (01) ◽  
pp. 101
Author(s):  
George W Rozakis ◽  
Sergey A Dzugan ◽  
◽  

Multimodal physiological medicine is the art of restoring physiology to youthful levels for the purpose of preventing and treating age-related diseases. Age-related macular degeneration (AMD) is presented as a disease that is caused by multiple errors of physiology including deficiencies of the steroidal hormones dehydroepiandrosterone (DHEA), pregnenolone, oestriol, oestradiol, oestrone, testosterone and progesterone as well as deficiencies in melatonin, zinc and other nutrients. It is proposed that multiple steroidal deficiency results in a compensatory attempt to synthesise hormones from cholesterol in the macula and that this conversion is dysfunctional in AMD, resulting in cholesterol-laden drusen. Furthermore, it is suggested that physiological errors indirectly lead to retinal pigment epithelial cell failure due to a decline in stem cell function. It is suggested that macular degeneration can be safely and more efficaciously treated with combinations of hormones, nutrients and vitamins and that such treatment strikes at the underlying cause(s) of the disease and may reduce associated cardiovascular risk.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Elzbieta Pawlowska ◽  
Joanna Szczepanska ◽  
Ali Koskela ◽  
Kai Kaarniranta ◽  
Janusz Blasiak

Age-related macular degeneration (AMD) is a multifactorial disease of the retina featured by degeneration and loss of photoreceptors and retinal pigment epithelium (RPE) cells with oxidative stress playing a role in its pathology. Although systematic reviews do not support the protective role of diet rich in antioxidants against AMD, dietary polyphenols (DPs) have been reported to have beneficial effects on vision. Some of them, such as quercetin and cyanidin-3-glucoside, can directly scavenge reactive oxygen species (ROS) due to the presence of two hydroxyl groups in their B ring structure. Apart from direct ROS scavenging, DPs can lower oxidative stress in several other pathways. Many DPs induce NRF2 (nuclear factor, erythroid 2-like 2) activation and expression of phase II enzymes that are under transcriptional control of this factor. DPs can inhibit A2E photooxidation in RPE cells, which is a source of oxidative stress. Anti-inflammatory action of DPs in RPE cells is associated with regulation of various interleukins and signaling pathways, including IL-6/JAK2 (Janus kinase 2)/STAT3. Some DPs can improve impaired cellular waste clearance, including AMD-specific deficient phagocytosis of the Aβ42 peptide and autophagy.


2019 ◽  
Vol 20 (13) ◽  
pp. 3367 ◽  
Author(s):  
Chawanphat Muangnoi ◽  
Umar Sharif ◽  
Pahweenvaj Ratnatilaka Na Bhuket ◽  
Pornchai Rojsitthisak ◽  
Luminita Paraoan

Oxidative stress-induced damage to the retinal pigmented epithelium (RPE), a specialised post-mitotic monolayer that maintains retinal homeostasis, contributes to the development of age-related macular degeneration (AMD). Curcumin (Cur), a naturally occurring antioxidant, was previously shown to have the ability to protect RPE cells from oxidative stress. However, poor solubility and bioavailability makes Cur a poor therapeutic agent. As prodrug approaches can mitigate these limitations, we compared the protective properties of the Cur prodrug curcumin diethyl disuccinate (CurDD) against Cur in relation to oxidative stress induced in human ARPE-19 cells. Both CurDD and Cur significantly decreased H2O2-induced reactive oxygen species (ROS) production and protected RPE cells from oxidative stress-induced death. Both drugs exerted their protective effects through the modulation of p44/42 (ERK) and the involvement of downstream molecules Bax and Bcl-2. Additionally, the expression of antioxidant enzymes HO-1 and NQO1 was also enhanced in cells treated with CurDD and Cur. In all cases, CurDD was more effective than its parent drug against oxidative stress-induced damage to ARPE-19 cells. These findings highlight CurDD as a more potent drug compared to Cur against oxidative stress and indicate that its protective effects are exerted through modulation of key apoptotic and antioxidant molecular pathways.


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