Towards an In Vitro Retinal Model to Study and Develop New Therapies for Age-Related Macular Degeneration (original) (raw)
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International Journal of Biomedical Engineering and Technology, 2020
Age related macular degeneration (AMD) is a common disease that is prevalent among people of age 50. It is characterised by the loss of retinal pigment epithelial (RPE) cells from the macula of eye due to the deposition of drusen in the Bruch's membrane that supports the RPE cells. Treatment for AMD is to replace Bruch's membrane with scaffolds that provide conducive environment for the RPE cells to adhere and proliferate. In this study, a scaffold made of porous poly (caprolactone) (PCL) was designed using the tool COMSOL Multiphysics and its properties like structural integrity and the fluid flow were analysed using Brinkman's equation. The model has a square geometry with a dimension of 100 × 100 × 4 µm through which blood was allowed to flow from bottom to top across the geometry. The analysis was carried out for scaffolds with different porosity. The results show that the scaffold with higher porosity has a lower pressure gradient which is necessary for RPE cell adherence and is mechanically stable. This proves that a PCL scaffold with higher porosity is a potential replacement for Bruch's membrane.
Scientific Reports, 2022
The common retinal diseases are age-related macular degeneration (AMD) and retinitis pigmentosa (RP). They are usually associated with the dysfunction of retinal pigment epithelial (RPE) cells and degeneration of underlying Bruch's membrane. The RPE cell transplantation is the most promising therapeutic option to restore lost vision. This study aimed to construct an ultrathin porous fibrous film with properties similar to that of native Bruch's membrane as carriers for the RPE cells. Human amniotic membrane powder (HAMP)/Polycaprolactone (PCL) scaffolds containing different concentrations of HAMP were fabricated by electrospinning technique. The results showed that with increasing the concentration of HAMP, the diameter of fibers increased. Moreover, hydrophilicity and degradation rate were improved from 119° to 92° and 14 to 56% after 28 days immersion in phosphate-buffered saline (PBS) solution, respectively. All scaffolds had a porosity above 85%. Proper cell adhesion was obtained one day after culture and no toxicity was observed. However, after seven days, the rate of growth and proliferation of ARPE-19 cells, a culture model of RPE, on the PCL-30HAMP scaffold (HAMP concentration in PCL 7.2% by weight) was higher compared to other scaffolds. These results indicated that PCL-30HAMP fibrous scaffold has a great potential to be used in retinal tissue engineering applications. Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in individuals over 50 1. Due to the increase of the aging population, the incidence and burden of AMD are expected to increase alarmingly in the coming years 2. Retinitis pigmentosa (RP) prevalence is approximately 1 in 5000 individuals 3,4. The diseases are characterized by the degeneration of a specific cell layer at the back of the eye, the retinal pigment epithelium, which is essential in retinal function 5. So far, no efficient treatment has been provided for these diseases. Gene therapy and anti-angiogenic drugs just delay the progression of these diseases. One of the best treatments is to replace the destructed cells with new RPE ones 6,7. Cell transplantation may have the potential for retinal regeneration. However, several problems hinder the successful repair of the retina including disorganized or misplaced grafts, as well as reflux of the cells from the injection site, which might lead to serious complications including RPE cell stacking, cell death, and retinal fibrosis. Recent studies have shown that the use of scaffolds can address these obstacles 8,9. The RPE cells are located between the photoreceptors and the underlying Bruch's membrane (BM) which separates the RPE from the blood vessels of the choroid. It is an extracellular matrix with a thickness of 2-4.7 µm that acts as a molecular sieve to maintain the metabolic exchange between the vasculature and outer retina 5,10. Since in AMD the underlying BM is often compromised, the thin scaffold can further act as a prosthetic BM, ensuring the survival, integrity, and functionality of the attached RPE cell monolayer 5. Various membranes have been used as scaffolds for RPE cells, but long-term cell viability and functionality are still largely unknown 9 .
Science translational medicine, 2018
Retinal pigment epithelium (RPE) dysfunction and loss are a hallmark of non-neovascular age-related macular degeneration (NNAMD). Without the RPE, a majority of overlying photoreceptors ultimately degenerate, leading to severe, progressive vision loss. Clinical and histological studies suggest that RPE replacement strategies may delay disease progression or restore vision. A prospective, interventional, U.S. Food and Drug Administration-cleared, phase 1/2a study is being conducted to assess the safety and efficacy of a composite subretinal implant in subjects with advanced NNAMD. The composite implant, termed the California Project to Cure Blindness-Retinal Pigment Epithelium 1 (CPCB-RPE1), consists of a polarized monolayer of human embryonic stem cell-derived RPE (hESC-RPE) on an ultrathin, synthetic parylene substrate designed to mimic Bruch's membrane. We report an interim analysis of the phase 1 cohort consisting of five subjects. Four of five subjects enrolled in the study ...
Journal of Ophthalmology, 2014
Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein.
Journal of biomedical materials research. Part A, 2016
Deterioration of retina and death of the retinal cells due to age, diabetes or occlusion can cause retinal degeneration which leads to loss of vision. In this study, it is aimed to design a bilayered matrix to mimic the choroid and the Bruch's membrane of the retinal tissue. As choroid, a microchannelled network resembling a fractal tree design was fabricated by photolithography over photocrosslinkable methacrylated hyaluronic acid hydrogel (HAMA). Gelatin or collagen was immobilized into the microchannels to enhance adherence of Human Umbilical Vein Endothelial Cells (HUVEC). At late culture periods (2 weeks), formation of tubular structures due to proliferation of the attached cells was observed. As Bruch's membrane, an electrospun fibroin nanofiber mat was produced to grow retinal pigment epithelium (RPE) cells on. Cellular interactions between RPE and HUVEC in the microchannels were investigated in a co-culture model in a non-contact mode. It was deduced that by combinin...
Frontiers in Bioengineering and Biotechnology, 2020
Age-related Macular Degeneration (AMD) is an up-to-date untreatable chronic neurodegenerative eye disease of multifactorial origin, and the main causes of blindness in over 65 y.o. people. It is characterized by a slow progression and the presence of a multitude of factors, highlighting those related to diet, genetic heritage and environmental conditions, present throughout each of the stages of the illness. Current therapeutic approaches, mainly consisting on intraocular drug delivery, are only used for symptoms relief and/or to decelerate the progression of the disease. Furthermore, they are overly simplistic and ignore the complexity of the disease and the enormous differences in the symptomatology between patients. Due to the wide impact of the AMD and the up-to-date absence of clinical solutions, Due to the wide impact of the AMD and the up-to-date absence of clinical solutions, different treatment options have to be considered. Cell therapy is a very promising alternative to d...
Tissue Engineering Strategies for Retina Regeneration
Applied Sciences
The retina is a complex and fragile photosensitive part of the central nervous system which is prone to degenerative diseases leading to permanent vision loss. No proven treatment strategies exist to treat or reverse the degenerative conditions. Recent investigations demonstrate that cell transplantation therapies to replace the dysfunctional retinal pigment epithelial (RPE) cells and or the degenerating photoreceptors (PRs) are viable options to restore vision. Pluripotent stem cells, retinal progenitor cells, and somatic stem cells are the main cell sources used for cell transplantation therapies. The success of retinal transplantation based on cell suspension injection is hindered by limited cell survival and lack of cellular integration. Recent advances in material science helped to develop strategies to grow cells as intact monolayers or as sheets on biomaterial scaffolds for transplantation into the eyes. Such implants are found to be more promising than the bolus injection ap...
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 2016
Clinical-grade manufacturing of a functional retinal pigment epithelium (RPE) monolayer requires reproducing, as closely as possible, the natural environment in which RPE grows. In vitro, this can be achieved by a tissue engineering approach, in which the RPE is grown on a nanofibrous biological or synthetic scaffold. Recent research has shown that nanofiber scaffolds perform better for cell growth and transplantability compared with their membrane counterparts and that the success of the scaffold in promoting cell growth/function is not heavily material dependent. With these strides, the field has advanced enough to begin to consider implementation of one, or a combination, of the tissue engineering strategies discussed herein. In this study, we review the current state of tissue engineering research for in vitro culture of RPE/scaffolds and the parameters for optimal scaffold design that have been uncovered during this research. Next, we discuss production methods and manufacturer...