Triptonide protects retinal cells from oxidative damage via activation of Nrf2 signaling.

Age­related macular degeneration (AMD) is an ocular disease that threatens the visual function of older adults worldwide. Key pathological processes involved in AMD include oxidative stress, inflammation and choroidal vascular dysfunction. Retinal pigment epithelial cells and Müller cells are most susceptible to oxidative stress. Traditional herbal medicines are increasingly being investigated in the field of personalized medicine in ophthalmology. Triptonide (Tn) is a diterpene tricyclic oxide, the main active ingredient in the extract from the Chinese herbal medicinal plant Tripterygium wilfordii, and is considered an effective immunosuppressant and anti­inflammatory drug. The present study investigated the potential beneficial role of Tn in retinal oxidative damage in order to achieve personalized treatment for early AMD. An oxidative stress model of retinal cells induced by H2O2 and a retinal injury model of mice induced by light and N­Methyl­D­aspartic acid were constructed. In vitro, JC­1 staining, flow cytometry and apoptosis assay confirmed that low concentrations of Tn effectively protected retinal cells from oxidative damage, and reverse transcription­quantitative PCR and western blotting analyses revealed that Tn reduced the expression of retinal oxidative stress­related genes and inflammatory factors, which may depend on the PI3K/AKT/mTOR­induced Nrf2 signaling pathway. In vivo, by retinal immunohistochemistry, hematoxylin and eosin staining and electroretinogram assay, it was found that retinal function and structure improved and choroidal neovascularization was significantly inhibited after Tn pretreatment. These results suggested that Tn is an efficient Nrf2 activator, which can be expected to become a new intervention for diseases such as AMD, to inhibit retinal oxidative stress damage and pathological neovascularization.

Towards Stem/Progenitor Cell-Based Therapies for Retinal Degeneration.

Retinal degeneration (RD) is a leading cause of blindness worldwide and includes conditions such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), and Stargardt's disease (STGD). These diseases result in the permanent loss of vision due to the progressive and irreversible degeneration of retinal cells, including photoreceptors (PR) and the retinal pigment epithelium (RPE). The adult human retina has limited abilities to regenerate and repair itself, making it challenging to achieve complete self-replenishment and functional repair of retinal cells. Currently, there is no effective clinical treatment for RD. Stem cell therapy, which involves transplanting exogenous stem cells such as retinal progenitor cells (RPCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs), or activating endogenous stem cells like Müller Glia (MG) cells, holds great promise for regenerating and repairing retinal cells in the treatment of RD. Several preclinical and clinical studies have shown the potential of stem cell-based therapies for RD. However, the clinical translation of these therapies for the reconstruction of substantial vision still faces significant challenges. This review provides a comprehensive overview of stem/progenitor cell-based therapy strategies for RD, summarizes recent advances in preclinical studies and clinical trials, and highlights the major challenges in using stem/progenitor cell-based therapies for RD.

Development and Characterization of Modified Chitosan Lipopolyplex for an Effective siRNA Delivery.

Cytotoxicity, speedy degradation, and limited cellular absorption are the foremost features influencing the successful delivery of RNAs. Chitosan (Cs) is a polymer that offers an advantage due to its bio-compatibility and biodegradable nature, making it an ideal polycationic vector for delivering siRNA. In this study, chitosan has been modified with arginine in order to increase its encapsulation of siRNA and improve cellular absorption. It was discovered that arginine and guanidino moieties could transport through membranes of cells and play an important part in membrane permeability. FTIR and 13C NMR were used to characterize the complex. These chitosan-arginine (CsAr) siRNA complexes are further encapsulated in anionic DPPC/cholesterol liposomes to combine the effects of liposome-chitosan-arginine complexes called lipopolyplexes (LCAr). Formed LCAr were investigated for their lipid/CsAr-siRNA ratios, size, zeta-potential, heparin, and serum RNase stability by agarose gel retardation, and cell uptake efficiency compared to their "parent" polyplexes. Results revealed complete lipidation of CsAr-siRNA polyplexes at lipid mass ratio 10 resulting in lipopolyplexes in the 120 to 230nm range. Polyplex entrapped ~70% of siRNA, whereas lipidation increases siRNA encapsulation to ~95%. Developed LCAr showed ~4 times less hemolytic potential as compared to the parent polyplexes at the highest siRNA dose. The CsAr-siRNA and its lipid-coated form showed enhanced cellular association as compared to the marketed Lipofectamine 2000 proving its effectiveness in siRNA delivery. CsAr-liposome conjugation is simple and safe, and serves as a robust carrier for gene transport in physiological situations without compromising transfection efficacy.

Evaluating the protective effects of dexamethasone and electrospun mesh combination on primary human mixed retinal cells under hyperglycemic stress.

Chronic inflammation is a leading cause of neurodegeneration and vision loss in hyperglycemia-associated conditions such as diabetic retinopathy. Corticosteroid injections are widely used for treatment but suffer from limitations such as rapid drug clearance, short drug half-lives and frequent administration. While drug release from biomaterial carriers can overcome these shortcomings, evaluating the combined effects of corticosteroids and polymeric matrices under hyperglycemic stress is an important step towards aiding translation. In this study, we investigated the effects of dexamethasone (DEX) and electrospun mesh combination on primary human mixed retinal cells under normal and hyperglycemic culture conditions. DEX-incorporated poly(lactide-co-glycolide) (PLGA) meshes were prepared and characterized for architecture, chemistry, drug distribution and in vitro release. The meshes exhibited cumulative in vitro drug release of 39.5 % over 2 months at a near constant rate. Under normal culture conditions, DEX-PLGA meshes promoted significantly higher viability of mixed retinal cells than the control groups but without adverse phenotypic activation. Under hyperglycemic conditions, DEX supplementation resulted in higher viability than the control, although the highest viability was achieved only when DEX was added to cells cultured on PLGA fibers. The combination of DEX and PLGA fibers also promoted higher mRNA expression of the antioxidant GSH under hyperglycemia. Importantly, the largest reduction in the production of pro-inflammatory cytokines viz., MMP-9, IL-6, IL-8 and VEGF-R1 was observed for the DEX and PLGA combination. Our study reveals a combined effect of DEX and electrospun fibers in combating hyperglycemia-driven pro-inflammatory responses, which can aid the development of DEX-loaded electrospun implants for diabetes-driven retinal conditions.

Deficiency of copper responsive gene stmn4 induces retinal developmental defects.

As part of the central nervous system (CNS), the retina senses light and also conducts and processes visual impulses. The damaged development of the retina not only causes visual damage, but also leads to epilepsy, dementia and other brain diseases. Recently, we have reported that copper (Cu) overload induces retinal developmental defects and down-regulates microtubule (MT) genes during zebrafish embryogenesis, but whether the down-regulation of microtubule genes mediates Cu stress induced retinal developmental defects is still unknown. In this study, we found that microtubule gene stmn4 exhibited obviously reduced expression in the retina of Cu overload embryos. Furthermore, stmn4 deficiency (stmn4-/-) resulted in retinal defects similar to those seen in Cu overload embryos, while overexpression of stmn4 effectively rescued retinal defects and cell apoptosis occurred in the Cu overload embryos and larvae. Meanwhile, stmn4 deficient embryos and larvae exhibited reduced mature retinal cells, the down-regulated expression of microtubules and cell cycle-related genes, and the mitotic cell cycle arrests of the retinal cells, which subsequently tended to apoptosis independent on p53. The results of this study demonstrate that Cu stress might lead to retinal developmental defects via down-regulating expression of microtubule gene stmn4, and stmn4 deficiency leads to impaired cell cycle and the accumulation of retinal progenitor cells (RPCs) and their subsequent apoptosis. The study provides a certain referee for copper overload in regulating the retinal development in fish.

Continuous non-adherent culture promotes transdifferentiation of human adipose-derived stem cells into retinal lineage.

Non-adherent culture is critical for the transdifferentiation of stem cells from mesoderm to neuroectoderm. Sphere culture has been reported to directly induce the adipose tissue cells to neural stem cells. Here we aimed to evaluate continuous non-adherent culture on the transdifferentiation potential of human adipose-derived stem cells (ASCs) into retinal lineage. Human ASCs were induced into retinal lineage by the treatment of noggin, dickkopf-related protein 1, and IGF-1 (NDI) under adherent and non-adherent culture. The NDI induction treatment with the adherent culture for 21 days promoted robust expression of retinal markers in the induced ASCs as compared to those without NDI induction on the adherent culture. With continuous non-adherent culture for 21 days, human ASCs could highly express retinal marker genes even without NDI induction treatment as compared to those on the adherent culture. The combination of continuous non-adherent culture with the NDI induction did not show a significant upregulation of the retinal marker expression as compared to either NDI induction with the adherent culture or continuous non-adherent culture without NDI induction treatment. In summary, both non-adherent culture and NDI induction medium could independently promote the transdifferentiation of human ASCs into retinal lineage. Yet, their combination did not produce an enhancement effect.

Therapeutic Potential of Oral-Derived Mesenchymal Stem Cells in Retinal Repair.

The retina has restricted regeneration ability to recover injured cell layer because of reduced production of neurotrophic factors and increased inhibitory molecules against axon regrowth. A diseased retina could be regenerated by repopulating the damaged tissue with functional cell sources like mesenchymal stem cells (MSCs). The cells are able to release neurotrophic factors (NFs) to boost axonal regeneration and cell maintenance. In the current study, we comprehensively explore the potential of various types of stem cells (SCs) from oral cavity as promising therapeutic options in retinal regeneration. The oral MSCs derived from cranial neural crest cells (CNCCs) which explains their broad neural differentiation potential and secret rich NFs. They are comprised of dental pulp SCs (DPSCs), SCs from exfoliated deciduous teeth (SHED), SCs from apical papilla (SCAP), periodontal ligament-derived SCs (PDLSCs), gingival MSCs (GMSCs), and dental follicle SCs (DFSCs). The Oral MSCs are becoming a promising source of cells for cell-free or cell-based therapeutic approach to recover degenerated retinal. These cells have various mechanisms of action in retinal regeneration including cell replacement and the paracrine effect. It was demonstrated that they have more neuroprotective and neurotrophic effects on retinal cells than immediate replacement of injured cells in retina. This could be the reason that their therapeutic effects would be weakened over time. It can be concluded that neuronal and retinal regeneration through these cells is most likely due to their NFs that dramatically suppress oxidative stress, inflammation, and apoptosis. Although, oral MSCs are attractive therapeutic options for retinal injuries, more preclinical and clinical investigations are required.

Human retinal secretome: A cross-link between mesenchymal and retinal cells.

In recent years, mesenchymal stem cells (MSC) have been considered the most effective source for regenerative medicine, especially due to released soluble paracrine bioactive components and extracellular vesicles. These factors, collectively called the secretome, play crucial roles in immunomodulation and in improving survival and regeneration capabilities of injured tissue. Recently, there has been a growing interest in the secretome released by retinal cytotypes, especially retinal pigment epithelium and Müller glia cells. The latter trophic factors represent the key to preserving morphofunctional integrity of the retina, regulating biological pathways involved in survival, function and responding to injury. Furthermore, these factors can play a pivotal role in onset and progression of retinal diseases after damage of cell secretory function. In this review, we delineated the importance of cross-talk between MSCs and retinal cells, focusing on common/induced secreted factors, during experimental therapy for retinal diseases. The cross-link between the MSC and retinal cell secretomes suggests that the MSC secretome can modulate the retinal cell secretome and vice versa. For example, the MSC secretome can protect retinal cells from degeneration by reducing oxidative stress, autophagy and programmed cell death. Conversely, the retinal cell secretome can influence the MSC secretome by inducing changes in MSC gene expression and phenotype.

Maillard Reaction Crosslinked Alginate-Albumin Scaffolds for Enhanced Fenofibrate Delivery to the Retina: A Promising Strategy to Treat RPE-Related Dysfunction.

There are limited treatments currently available for retinal diseases such as age-related macular degeneration (AMD). Cell-based therapy holds great promise in treating these degenerative diseases. Three-dimensional (3D) polymeric scaffolds have gained attention for tissue restoration by mimicking the native extracellular matrix (ECM). The scaffolds can deliver therapeutic agents to the retina, potentially overcoming current treatment limitations and minimizing secondary complications. In the present study, 3D scaffolds made up of alginate and bovine serum albumin (BSA) containing fenofibrate (FNB) were prepared by freeze-drying technique. The incorporation of BSA enhanced the scaffold porosity due to its foamability, and the Maillard reaction increased crosslinking degree between ALG with BSA resulting in a robust scaffold with thicker pore walls with a compression modulus of 13.08 KPa suitable for retinal regeneration. Compared with ALG and ALG-BSA physical mixture scaffolds, ALG-BSA conjugated scaffolds had higher FNB loading capacity, slower release of FNB in the simulated vitreous humour and less swelling in water and buffers, and better cell viability and distribution when tested with ARPE-19 cells. These results suggest that ALG-BSA MR conjugate scaffolds may be a promising option for implantable scaffolds for drug delivery and retinal disease treatment.

In vitro triple culture model of retinoblastoma for pre-clinical investigations.

BACKGROUND: Retinoblastoma (Rb) is a rare cancer of the retina that occurs during early childhood. The disease is relatively rare but aggressive, accounting for ∼3% of childhood cancers. Treatment modalities encompass the administration of large doses of chemotherapeutic drugs, which result in multiple side-effects. Therefore, it is essential to have safe and effective newer therapies and suitable physiologically relevant, alternative-to-animal, in vitro cell culture-based models to enable rapid and efficient evaluation of potential therapies. METHODOLOGY: This investigation was focused on the development of a triple co-culture model comprising Rb, retinal epithelium, and choroid endothelial cells, using a protein coating cocktail, to recapitulate this ocular cancer under in vitro conditions. This resulting model was used for screening drug toxicity, based on the growth profile of Rb cells, using carboplatin as the model drug. Further, a combination of bevacizumab and carboplatin was evaluated using the developed model, to lower the concentration of carboplatin and thereby reduce its physiological side-effects. MAJOR RESULTS: The effect of drug treatment on the triple co-culture was assessed by increase in the apoptotic profile of Rb cells. Further, the barrier properties were found to be lower with a decrease in the angiogenetic signals that included expression of vimentin. Measurement of cytokine levels signified reduced inflammatory signals due to the combinatorial drug treatment. CONCLUSIONS: These findings validated that the triple co-culture Rb model was suitable for evaluating anti-Rb therapeutics and could thereby decrease the immense load on animal trials, which are the primary screens employed for evaluating retinal therapies.

Induction of vascular endothelial growth factor-A165a in human retinal and endothelial cells in response to glyoxal.

Low-density lipoprotein (LDL) apheresis is effective and safe for patients with diabetes, proteinuria, and dyslipidemia. Diabetes mellitus is accompanied by ocular microvascular complications like retinal neovascularization or diabetic macular edema. These are leading causes of blindness and can be mediated by abnormal vessel growth and increased vascular permeability due to elevated levels of vascular endothelial growth factor (VEGF) in diabetic patients. In this study, we established methods to study the expression of different VEGF isoforms in human retinal and endothelial cells. The VEGF-A165a isoform is much higher expressed in retinal cells, compared to endothelial cells. Stimulation with glyoxal as a model of oxidative stress under diabetic conditions lead to a pronounced induction of VEGF-A165a in human retinal and endothelial cells. These data suggest that diabetes and oxidative stress induce VEGF-A isoforms which could be relevant in regulating the ingrowths of novel blood vessels into the retina in diabetic patients.

Cell Fate of Retinal Progenitor Cells: In Ovo UbC-StarTrack Analysis.

Clonal cell analysis outlines the ontogenic potential of single progenitor cells, allowing the elucidation of the neural heterogeneity among different cell types and their lineages. In this work, we analyze the potency of retinal stem/progenitor cells through development using the chick embryo as a model. We implemented in ovo the clonal genetic tracing strategy UbC-StarTrack for tracking retinal cell lineages derived from individual progenitors of the ciliary margin at E3.5 (HH21-22). The clonal assignment of the derived-cell progeny was performed in the neural retina at E11.5-12 (HH38) through the identification of sibling cells as cells expressing the same combination of fluorophores. Moreover, cell types were assessed based on their cellular morphology and laminar location. Ciliary margin derived-cell progenies are organized in columnar associations distributed along the peripheral retina with a limited tangential dispersion. The analysis revealed that, at the early stages of development, this region harbors multipotent and committed progenitor cells.

Bioengineering approaches for modelling retinal pathologies of the outer blood-retinal barrier.

Alterations of the junctional complex of the outer blood-retinal barrier (oBRB), which is integrated by the close interaction of the retinal pigment epithelium, the Bruch's membrane, and the choriocapillaris, contribute to the loss of neuronal signalling and subsequent vision impairment in several retinal inflammatory disorders such as age-related macular degeneration and diabetic retinopathy. Reductionist approaches into the mechanisms that underlie such diseases have been hindered by the absence of adequate in vitro models using human cells to provide the 3D dynamic architecture that enables expression of the in vivo phenotype of the oBRB. Conventional in vitro cell models are based on 2D monolayer cellular cultures, unable to properly recapitulate the complexity of living systems. The main drawbacks of conventional oBRB models also emerge from the cell sourcing, the lack of an appropriate Bruch's membrane analogue, and the lack of choroidal microvasculature with flow. In the last years, the advent of organ-on-a-chip, bioengineering, and stem cell technologies is providing more advanced 3D models with flow, multicellularity, and external control over microenvironmental properties. By incorporating additional biological complexity, organ-on-a-chip devices can mirror physiologically relevant properties of the native tissue while offering additional set ups to model and study disease. In this review we first examine the current understanding of oBRB biology as a functional unit, highlighting the coordinated contribution of the different components to barrier function in health and disease. Then we describe recent advances in the use of pluripotent stem cells-derived retinal cells, Bruch's membrane analogues, and co-culture techniques to recapitulate the oBRB. We finally discuss current advances and challenges of oBRB-on-a-chip technologies for disease modelling.

Single-cell transcriptomic analysis revealing changes in retinal cell subpopulation levels and the pathways involved in diabetic retinopathy.

Background: Diabetic retinopathy (DR) is a common microvascular complication of diabetes and one of the most common causes of visual impairment and blindness. However, it is not yet known how abnormal retinal cell subpopulations contribute to disease progression. Methods: In this study, we used the Gene Expression Omnibus database to construct a single-cell atlas of DR and healthy samples to explore changes in the abundance of different cell subpopulations, and identify the molecular pathways potentially involved in DR. Results: Our results showed that DR was associated with significantly reduced numbers of bipolar cells, Müller glia, retinal pigment epithelial cells, and cone photoreceptors, but was also associated with significantly greater numbers of pericytes, rod photoreceptors, anaplastic cells, and microglia. Our results suggest that subpopulations of Müller glia, microglia, endothelial cells, and bipolar cells in DR tissues may be involved in various oxidative stress- and inflammation-related pathways. Conclusions: In summary, we showed that Müller glia, endothelial cells, microglia, and bipolar cells in DR tissues are involved in oxidative stress- and inflammation-related pathways, which may contribute to the progression of the disease and ultimately lead to visual impairment and blindness. This study will provide a theoretical basis for further exploring the specific mechanism of DR.

Can pattern electroretinography be a relevant diagnostic aid in amblyopia? - A systematic review.

INTRODUCTION: Pattern Electroretinography (PERG) is a highly sensitive electrophysiological technique used as an indicator of changes in retinal macular area. Amblyopia seems to result from a cortical visual imbalance but changes at the retinal level may also be present. The purpose of this systematic review was to evaluate if there are any consistent changes described in the scientific literature in PERG responses of amblyopic eyes. MATERIALS AND METHODS: Searches were conducted in PubMed and Embase databases, using the keywords "Electroretinography" and "Amblyopia", combined with MeSH or Emtree terms "Pattern Electroretinography", "amblyopia", "PERG" and "amblyopia". PERG P50-N95 amplitude and P50 latency were analysed as well as the methodology used. RESULTS: A total of 234 articles were found and 6 articles were included for review. One of the articles reported results in adults and five of them in children. One of the articles in children reported no changes in either P50-N95 amplitude or P50 latency. All articles that described differences between the amblyopic eye and the normal eye found a decrease in P50-N95 amplitude and/or a delay in P50 latency. CONCLUSIONS: This review shows promising findings for the use of PERG in amblyopia as an aid in the diagnostic protocol, since this technique may be able to detect an apparent functional impairment of the amblyopic eye.

Single-Cell RNA-Seq Reveals the Cellular Diversity and Developmental Characteristics of the Retinas of an Infant and a Young Child.

The human retina, located in the innermost layer of the eye, plays a decisive role in visual perception. Dissecting the heterogeneity of retinal cells is essential for understanding the mechanism of visual development. Here, we performed single-cell RNA-seq to analyze 194,967 cells from the donors of infants and young children, resulting in 17 distinct clusters representing major cell types in the retina: rod photoreceptors (PRs), cone PRs, bipolar cells (BCs), horizontal cells (HCs), amacrine cells (ACs), retinal ganglion cells (RGCs), Müller glial cells (MGs), microglia, and astrocytes (ASTs). Through reclustering, we identified known subtypes of cone PRs as well as additional unreported subpopulations and corresponding markers in BCs. Additionally, we linked inherited retinal diseases (IRDs) to certain cell subtypes or subpopulations through enrichment analysis. We next constructed extensive intercellular communication networks and identified ligand-receptor interactions that play crucial roles in regulating neural cell development and immune homeostasis in the retina. Intriguingly, we found that the status and functions of PRs changed drastically between the young children and adult retina. Overall, our study offers the first retinal cell atlas in infants and young children dissecting the heterogeneity of the retina and identifying the key molecules in the developmental process, which provides an important resource that will pave the way for research on retinal development mechanisms and advancements in regenerative medicine concerning retinal biology.

Measures of disease activity in glaucoma.

Glaucoma is the leading cause of irreversible blindness globally which significantly affects the quality of life and has a substantial economic impact. Effective detective methods are necessary to identify glaucoma as early as possible. Regular eye examinations are important for detecting the disease early and preventing deterioration of vision and quality of life. Current methods of measuring disease activity are powerful in describing the functional and structural changes in glaucomatous eyes. However, there is still a need for a novel tool to detect glaucoma earlier and more accurately. Tear fluid biomarker analysis and new imaging technology provide novel surrogate endpoints of glaucoma. Artificial intelligence is a post-diagnostic tool that can analyse ophthalmic test results. A detail review of currently used clinical tests in glaucoma include intraocular pressure test, visual field test and optical coherence tomography are presented. The advanced technologies for glaucoma measurement which can identify specific disease characteristics, as well as the mechanism, performance and future perspectives of these devices are highlighted. Applications of AI in diagnosis and prediction in glaucoma are mentioned. With the development in imaging tools, sensor technologies and artificial intelligence, diagnostic evaluation of glaucoma must assess more variables to facilitate earlier diagnosis and management in the future.

Detection of Mycoplasma Contamination in Transplanted Retinal Cells by Rapid and Sensitive Polymerase Chain Reaction Test.

Contamination of cells/tissues by infectious pathogens (e.g., fungi, viruses, or bacteria, including mycoplasma) is a major problem in cell-based transplantation. In this study, we tested a polymerase chain reaction (PCR) method to provide rapid, simple, and sensitive detection of mycoplasma contamination in laboratory cultures for clinical use. This mycoplasma PCR system covers the Mycoplasma species (spp.) listed for testing in the 17th revision of the Japanese Pharmacopoeia, and we designed it for use in transplantable retinal cells. Here, we analyzed mycoplasma contamination in induced pluripotent stem cell (iPS cell)-derived transplantable retinal pigment epithelium (RPE) cells. In the spike tests to RPE cells with nine species of class Mollicutes bacteria, including seven Mycoplasma spp. and one of each Acholeplasma spp. and Ureaplasma spp., contamination at the concentration of 100 and 10 CFU/mL were detected with 100% probability in all cases, while 1 CFU/mL had a detection rate of 0-75%. DNA prepared from bacteria species other than class Mollicutes species was not detectable, indicating the specificity of this PCR. While iPS cells and iPS-RPE cells established in our laboratory were all negative by this PCR, some of the commercially available cell lines were positive. Cells for transplantation should never have infection, as once pathogens are implanted into the eyes, they can cause severe intraocular inflammation. Thus, it is imperative to monitor for infections in the transplants, although generally, mycoplasma infection is difficult to detect.

Apoptosis in health and diseases of the eye and brain.

Apoptosis is a form of programmed cell death (PCD) and enables the immunologically silent disposal of senescent or unwanted cells, causing minimal damage to the surrounding environment. Apoptosis can occur via intrinsic or extrinsic pathways that initiate a series of intracellular and extracellular signaling events. This ultimately leads to the clearance of the cell by phagocytes. This normal physiological mechanism may be accelerated in several diseases including those involving the eyes and brain, leading to loss of structure and function. This review presents the role of PCD in the health of the eyes and brain, and the evidence presented for its aberrant role in disease.

Mesenchymal Stem Cells: Signaling Pathways in Transdifferentiation Into Retinal Progenitor Cells.

Several signaling pathways and transcription factors control the cell fate in its in vitro development and differentiation. The orchestrated use of these factors results in cell specification. In coculture methods, many of these factors secrete from host cells but control the process. Today, transcription factors required for retinal progenitor cells are well known, but the generation of these cells from mesenchymal stem cells is an ideal goal. The purpose of the paper is to review novel methods for retinal progenitor cell production and selecting a set of signaling molecules in the presence of adult retinal pigment epithelium and extraocular mesenchyme acting as inducers of retinal cell differentiation.