Interferons in vitreoretinal diseases; a review on their clinical application, and mechanism of action.

PURPOSE: This review investigates the therapeutic benefits of interferons (IFNs) in vitreoretinal diseases, focusing on their regulatory roles in innate immunological reactions and angiogenesis. The study aims to categorize the clinical outcomes of IFN applications and proposes a molecular mechanism underlying their action. METHODS: A systematic review was conducted using MEDLINE/PubMed, Web of Science, EMBASE, and Google Scholar databases to identify randomized clinical trials, case series, and case-control studies related to IFNs' impact on vitreoretinal diseases (1990-2022). The data synthesis involved an in-depth analysis of the anti-inflammatory and anti-angiogenesis effects of IFNs across various studies. RESULTS: Our findings indicate that IFNs exhibit efficacy in treating inflammation-associated vitreoretinal disorders. However, a lack of sufficient evidence exists regarding the suitability of IFNs in angiogenesis-associated vitreoretinal diseases like choroidal neovascularization and diabetic retinopathies. The synthesis of data suggests that IFNs may not be optimal for managing advanced stages of angiogenesis-associated disorders. CONCLUSION: While IFNs emerge as promising therapeutic candidates for inflammation-related vitreoretinal diseases, caution is warranted in their application for angiogenesis-associated disorders, especially in advanced stages. Further research is needed to elucidate the nuanced molecular pathways of IFN action, guiding their targeted use in specific vitreoretinal conditions.

Effect of adalimumab as an anti-inflammatory agent on gene expression of retinal pigment epithelial cells.

Adalimumab (ADA) is an anti-inflammatory antibody that has FDA approval as a systemic medication for treating noninfectious uveitis. It is also provisionally being investigated as an intravitreal injection for various retinal conditions. This study aimed to assess the effect of ADA on apoptotic, inflammatory, and fibrogenesis gene expression at mRNA and protein levels in retinal pigment epithelial (RPE) cells. RPEs were treated with serial concentrations of ADA (0.5x, x, 2x, and 4x; [x = 250 µg/mL]) for 24 hours. MTT assay was done and the mRNA and protein expressions were quantified using real-time PCR and ELISA assay, respectively. The mRNA levels of IL-1b and IL-6 were significantly increased in ADA-treated RPEs at 0.5x and x concentrations. However, the increase in cytokine secretion was observed only in IL-1b at x concentration. TGF-ß was significantly upregulated in the 0.5x and 4x doses of ADA both at mRNA and protein levels. MTT assay, along with an unchanged BCL-2/BAX ratio confirmed the safety of ADA on RPEs at all studied concentrations. In conclusion, despite its safety, the 2x concentration of ADA was the only dose that did not ignite the expression of any of the studied inflammatory and fibrogenesis genes. This dosage, which is roughly equal to 2 mg intravitreal dose in a clinical setting, might be referred to as a reference starting point for future in-vivo studies in ocular conditions.

Characterization of Central and Nasal Orbital Adipose Stem Cells and their Neural Differentiation Footprints.

BACKGROUND: The unique potential of stem cells to restore vision and regenerate damaged ocular cells has led to the increased attraction of researchers and ophthalmologists to ocular regenerative medicine in recent decades. In addition, advantages such as easy access to ocular tissues, non-invasive follow-up, and ocular immunologic privilege have enhanced the desire to develop ocular regenerative medicine. OBJECTIVE: This study aimed to characterize central and nasal orbital adipose stem cells (OASCs) and their neural differentiation potential. METHODS: The central and nasal orbital adipose tissues extracted during an upper blepharoplasty surgery were explant-cultured in Dulbecco's Modified Eagle Medium (DMEM)/F12 supplemented with 10% fetal bovine serum (FBS). Cells from passage 3 were characterized morphologically by osteogenic and adipogenic differentiation potential and by flow cytometry for expression of mesenchymal (CD73, CD90, and CD105) and hematopoietic (CD34 and CD45) markers. The potential of OASCs for the expression of NGF, PI3K, and MAPK and to induce neurogenesis was assessed by real-time PCR. RESULTS: OASCs were spindle-shaped and positive for adipogenic and osteogenic induction. They were also positive for mesenchymal and negative for hematopoietic markers. They were positive for NGF expression in the absence of any significant alteration in the expression of PI3K and MAPK genes. Nasal OASCs had higher expression of CD90, higher potential for adipogenesis, a higher level of NGF expression under serum-free supplementation, and more potential for neuron-like morphology. CONCLUSION: We suggested the explant method of culture as an easy and suitable method for the expansion of OASCs. Our findings denote mesenchymal properties of both central and nasal OASCs, while mesenchymal and neural characteristics were expressed stronger in nasal OASCs when compared to central ones. These findings can be added to the literature when cell transplantation is targeted in the treatment of neuro-retinal degenerative disorders.

Effect of adlay seed extract on inflammation and fibrogenesis in human corneal activated keratocytes at transcriptional level.

Corneal activated keratocytes (CAKs) -representing the injured phenotype of corneal stromal cells- are associated with several corneal diseases. Inflammatory cytokines are the key drivers of CAK formation subsequently leading to fibrogenesis. This study aimed to investigate the effect of adlay seed extract on the expression of genes involved in inflammation (IL-6, IL-1b, LIF) and fibrogenesis (TGF-ß) in CAK cells. CAKs (106 cells/10 cm2) were exposed to methanolic (MeOH) and residual (Res) extract of adlay seed (1 mg/ml, 24 h). The control group received the vehicle solution without extract at the same time and condition. Then, RNA extraction, cDNA synthesis, and real-time PCR were performed to quantify the relative expression of IL-6, IL-1b, LIF, and TGF-ß in the treated vs. control cells. This study showed that the MeOH extract of adlay seed could significantly downregulate the expression of IL-6 and IL-1b in the CAKs, while the Res extract led to a significant decrease in TGF-ß gene expression. We showed that CAK treatment with adlay seed extract could decrease the expression of genes related to inflammation and fibrogenesis. However, the genes to be targeted depended on the method of extraction. This proof-of-concept study could provide groundwork for the treatment of corneal stromal diseases and ocular regenerative medicine in the future.

Intra-stromal injection of honey-treated keratocytes as a cell-based therapy for experimental corneal laceration.

OBJECTIVES: This study aimed to investigate the potential of honey-supplemented medium (HSM) for expanding corneal keratocytes and its transplantation in a model of corneal laceration. METHODS: Keratocytes were cultured in 1 % HSM- or 10 % fetal bovine serum (FBS)-supplemented medium for 24 h. The effect of HSM on keratocyte proliferation was evaluated using the MTT assay. The relative expression of Lum, Kera, and ALDH3A1, known markers of native keratocytes, was quantified by real-time PCR. The safety and efficacy of HSM-treated keratocyte intrastromal injection in a rabbit model of corneal laceration were also evaluated. RESULTS: The MTT assay showed that HSM treatment did not significantly affect cell viability compared to FBS-supplemented medium (84.71 ± 2.38 vs. 100.08 ± 10.92, respectively; p=0.076). Moreover, HSM-treated keratocytes had significantly increased expression of Lum, Kera, and ALDH3A1 compared to cells treated with FBS, while the expression of the proliferation biomarker Thy-1 did not significantly differ between the two treatments. Intrastromal injection of HSM-treated keratocytes in the laceration animal model was safe and uneventful, resulting in less stromal inflammation and neovascularization, and consequently, better final architecture with less residual haze compared to the group injected with FBS-treated keratocytes. CONCLUSIONS: These findings suggest that honey is a suitable supplement for keratocyte treatment and corneal cell therapy. The use of HSM may have potential applications in the treatment of corneal injuries and diseases.

In Vitro Evaluation of Apoptosis, Inflammation, Angiogenesis, and Neuroprotection Gene Expression in Retinal Pigmented Epithelial Cell Treated with Interferon α-2b.

Angiogenesis, retinal neuropathy, and inflammation are the main molecular features of diabetic retinopathy (DR) and should be taken into consideration for potential treatment approaches. Retinal pigmented epithelial (RPE) cells play a major role in DR progression. This study evaluated the in vitro effect of interferon (IFN) α-2b on the expression of genes involved in apoptosis, inflammation, neuroprotection, and angiogenesis in RPE cells. RPE cells were cocultured with IFN α-2b at 2 doses (500 and 1,000 IU) and treatment periods (24 and 48 h). The quantitative relative expression of genes (BCL-2, BAX, BDNF, VEGF, and IL-1b) was evaluated in the treated versus control cells through real-time polymerase chain reaction (PCR). The result of this study demonstrated that IFN treatment at 1,000 IU (48 h) led to significant upregulation of BCL-2, BAX, BDNF, and IL-1b; however, the BCL-2/BAX ratio was not statistically altered from 1:1, in any of the treatment patterns. We also showed that VEGF expression was downregulated in RPE cells treated with 500 IU for 24 h. It can be concluded that IFN α-2b was safe (BCL-2/BAX ∼1:1) and enhanced neuroprotection at 1,000 IU (48 h); however-at the same time-IFN α-2b induced inflammation in RPE cells. Moreover, the antiangiogenic effect of IFN α-2b was solely observed in RPE cells treated with 500 IU (24 h). It seems that IFN α-2b in lower doses and short duration exerts antiangiogenic effects and in higher doses and longer duration has neuroprotective and inflammatory effects. Hence, appropriate concentration and duration of treatment, according to the type and stage of the disease, should be considered to achieve success in IFN therapy.

Human Wharton's Jelly Mesenchymal Stem Cell Secretome Modifies the Processes of Neuroprotection and Epithelial-Mesenchymal Transition in Retinal Pigment Epithelium at Transcriptional Level.

BACKGROUND: Retinal pigment epithelium (RPE) cells are potential targets for treating retinal detachment (RD) and proliferative vitreoretinopathy (PVR), considering the importance of neuroprotection and epithelial-mesenchymal transition (EMT) of RPE in these conditions. This study investigated the effect of human Wharton's jelly mesenchymal stem cell secretome (WJMSC-S) on the expression of genes involved in both neuroprotection and EMT in RPE cells in vitro (TRKB, MAPK, PI3K, BDNF, and NGF). METHODS: RPE cells from passages 5-7 were treated with WJMSC-S (or the vehicle culture medium as control) for 24 h at 37◦C and subsequently subjected to RNA extraction and cDNA synthesis. Gene expression level was evaluated using real-time PCR in the treated versus control cells. RESULTS: The results of our study showed that WJMSC-S led to a significant downregulation in three out of five studied gene expression (MAPK, TRKB, and NGF), and simultaneously, remarkably upregulated the expression of the BDNF gene. CONCLUSIONS: According to the present data, WJMSC-S can affect the EMT and neuroprotection processes at the mRNA level by suppressing EMT and promoting neuroprotection in RPE cells. This finding may have positive clinical implications in the context of RD and PVR.

A review on the effect of garlic on diabetes, BDNF, and VEGF as a potential treatment for diabetic retinopathy.

BACKGROUND: Garlic is one of the favorite herbs in traditional medicine that has been reported to have many medicinal features. The aim of the current study is to review the latest documents on the effect of garlic on diabetes, VEGF, and BDNF and, finally, to review the existing studies on the effect of garlic on diabetic retinopathy. MAIN TEXT: The therapeutic effect of garlic on diabetes has been investigated in various studies. Diabetes, especially in advanced stages, is associated with complications such as diabetic retinopathy, which is caused by the alteration in the expression of molecular factors involved in angiogenesis, neurodegeneration, and inflammation in the retina. There are different in-vitro and in-vivo reports on the effect of garlic on each of these processes. Considering the present concept, we extracted the most related English articles from Web of Science, PubMed, and Scopus English databases from 1980 to 2022. All in-vitro and animal studies, clinical trials, research studies, and review articles in this area were assessed and classified. RESULT AND CONCLUSION: According to previous studies, garlic has been confirmed to have beneficial antidiabetic, antiangiogenesis, and neuroprotective effects. Along with the available clinical evidence, it seems that garlic can be suggested as a complementary treatment option alongside common treatments for patients with diabetic retinopathy. However, more detailed clinical studies are needed in this field.

The efficacy of oral pain relief cocktail during pan-retinal photocoagulation for diabetic retinopathy: a randomized clinical trial.

PURPOSE: to evaluate the pain-relieving effect of analgesic combinations during pan-retinal photocoagulation (PRP) in patients with non-proliferative diabetic retinopathy (NPDR). METHODS: This study was a randomized, double-blind, placebo-controlled trial. Patients with severe NPDR without previous history of PRP were included in the study. Both eyes of the patients were treated with a pan-retinal photocoagulation procedure. The retina was divided into four quadrants and the treatment plan for patients submitted to PRP was divided into four sessions. Different oral medications were given to patients 1 hour before the procedure. Capsules containing a combination of analgesic drugs (including 325 mg acetaminophen, 200 mg ibuprofen, and 40 mg caffeine, referred to as N), pregabalin capsules (75 mg, referred to as P), a combination of N capsules and P capsules (referred to as NP), and the placebo were used in each session. Each patient scored the pain sensation immediately after the procedure using a visual analog scale (VAS). RESULT: 60 eyes of 30 patients were studied. The mean value of VAS in patients receiving the placebo was 3.3 ± 1.822 units, while this scale was 3.067 ± 1.507, 3.5 ± 1.479, and 3.5 ± 1.77 in the N, P, and NP consumed patients, respectively. There was no significant difference in VAS levels and the patient's vital signs between different sessions (P = 0.512). CONCLUSION: No evidence of the pain-relieving effect of N, P or NP was found during PRP. TRIAL REGISTRATION: IRCT20200915048724N1. Registered 20 October 2020, https://www.irct.ir/trial/51345.

A Review on the Application of Stem Cell Secretome in the Protection and Regeneration of Retinal Ganglion Cells; a Clinical Prospect in the Treatment of Optic Neuropathies.

PURPOSE: Retinal ganglion cells (RGCs) are one the most specialized neural tissues in the body. They transmit (and further process) chemoelectrical information originating in outer retinal layers to the central nervous system. In fact, the optic nerve is composed of RGC axons. Like other neural cells, RGCs will not completely heal after the injury, leading to irreversible vision loss from disorders such as glaucoma that primarily affect these cells. Several methods have been developed to protect or regenerate RGCs during or after the insult has occurred. This study aims to review the most recent clinical, animal and laboratory experiments designed for the regeneration of RGC that apply the stem cell-derived secretome. METHODS: We extracted the studies from Web of Science (ISI), Medline (PubMed), Scopus, Embase, and Google scholar from the first record to the last report registered in 2022, using the following keywords; "secretome" OR "conditioned medium" OR "exosome" OR "extracellular vesicle" AND "stem cell" AND "RGC" OR "optic neuropathy". Any registered clinical trials related to the subject were also extracted from clinicaltrial.gov. All published original studies that express the effect of stem cell secretome on RGC cells in optic neuropathy, whether in vitro, in animal studies, or in clinical trials were included in this survey. RESULTS: In this review, we provided an update on the existing reports, and a brief description of the details applied in the procedure. Compared to cell transplant, applying stem cell-derived secretome has the advantage of minimized immunogenicity yet preserving efficacy via its rich content of growth factors. CONCLUSIONS: Different sources of stem cell secretomes have distinct implications in the management of RGC injury, which is the main subject of the present article.

Evaluation of the Effect of Garlic Tablet as a Complementary Treatment for Patients with Diabetic Retinopathy.

Purpose: The aim of this study was to investigate the effectiveness of garlic (Allium sativum L.) tablets as a complimentary herbal medication in diabetic macular edema. Methods: A total of 91 diabetic participants (117 eyes) with central involved macular edema underwent a double-blind randomized trial. The patients used garlic tablets (500 mg) (2 tab/day) or placebo for 4 weeks and subsequently were examined by an expert ophthalmologist. Clinical manifestations including the best-corrected visual acuity (BCVA, logMAR), central macular thickness (CMT, µm), and intraocular pressure (IOP) were measured as the main outcomes. Results: BCVA was significantly improved by a 0.18 decrease in mean logMAR value in the garlic-treated patients in comparison with 0.06 in the control ones (P value = 0.027). CMT was decreased in both groups by a 102.99 µm decrease in the garlic group compared to 52.67 µm in the placebo group, albeit in a nonsignificant manner (P value: 0.094). IOP was decreased in the garlic group by 1.03 mmHg (P value: 0.024) and increased by 0.3 mmHg (P value: 0.468) in the placebo group. Conclusion: Our trial suggests that garlic supplements can improve visual acuity, decrease the CMT and lower the IOP, and can be considered as an adjuvant treatment in patients with diabetic macular edema. Garlic was satisfactorily tolerated in diabetic patients, and no significant adverse effect interrupting the safety profile was observed.

Assessment of macular findings by OCT angiography in patients without clinical signs of diabetic retinopathy: radiomics features for early screening of diabetic retinopathy.

This cross-sectional study aimed to quantitatively analyze the optical coherence tomography angiography (OCTA) images using MATLAB-based software and evaluate the initial changes in macular vascular density and the distortion of the foveal avascular zone (FAZ), before the clinical appearance of diabetic retinopathy. For this purpose, 21 diabetic patients without any clinical features indicating DR, and 21 healthy individuals matched with patients based on their demographic characteristics were included. Macular thickness, macular vascular density, and morphological changes of FAZ were assessed using OCTA. The diagnostic ability of morphological parameters was evaluated by receiver operating curve analysis. The intraclass correlation coefficient (ICCC) index was used to check the consistency of the extracted values. There was no significant difference in age, gender, LogMAR visual acuity, spherical equivalent, and intra-ocular pressure amongst patients and controls. No correlation was found between age and the FAZ area as well as vascular density. The vascular structure of the superficial layer showed FAZ enlargement, reduced vascular density in the macular area, and significant deviations of FAZ shape parameters (convexity and Frequency Domain Irregularity) in patients compared with healthy individuals. Measurements were highly correlated between separate imaging sessions with ICCC of over 0.85 for all parameters. The represented data suggests that radiomics parameters can be applied as both an early screening tool and guidance for better follow-up of diabetic patients who have not had any sign of DR in fundoscopic exams.

RPE based gene and cell therapy for inherited retinal diseases: A review.

The Retinal Pigment Epithelium (RPE) is the supportive layer located beneath the neural retina. Its health is essential for the proper function of photoreceptors. Indeed, any condition involving the RPE has the potential to induce an antegrade degeneration of the photoreceptors and inner retinal layers. Traditionally, degenerative disorders of the neural retina have been considered untreatable. However, the advent of gene and cell replacement therapies brings hope to halt or even cure retinal degenerative diseases. This study aims to review the most recent clinical trials registered on the RPE-based gene/cell intervention for the treatment of inherited retinal diseases (IRD). In this review, we provided an update on the clinical studies on the RPE-based gene/cell therapy for the treatment of IRD, summarized recent studies in this regard, and present the results of the corresponding clinical trials. A brief description of the details applied in the techniques, the advantages and withdraws of the utilized strategies were also included. This study provided evidence to show that gene therapy and cell replacement therapy have a great potential to become a successful treatment for IRD in the following decades, however, future studies should focus on novel methods to increase the safety and efficacy of the treatment.

Glutathione S-Transferase Omega-2 and Transforming Growth Factor-ß1 Polymorphisms in Iranian Glaucoma Patients.

BACKGROUND: To investigate the association of glutathione s-transferase omega 2 (GSTO2) (142N > D) and transforming growth factor-ß1 (TGF-ß1) (869T > C) gene polymorphisms on the pathogenesis of two common types of glaucoma (including primary open-angle glaucoma (POAG) and chronic angle-closure glaucoma (CACG)) in the Iranian population. METHODS: A total of 100 glaucoma patients (60% males and 40% females with an age mean ± SD of 34.66 ± 14.25 years; 56 cases of POAG and 44 cases of CACG) were enrolled in this study. GSTO2 (142N > D) and TGF-ß1 (869T > C) polymorphisms were evaluated by PCR-based methods in patients and controls. RESULTS: At locus GSTO2 (142N > D), the odds of ND genotype with respect to DD and NN genotypes were 1.55 and 2.08 times higher in POAG and CACG patients compared to those of patients in the control group (95% CI1: 0.80-2.98; 95% CI2: 1.00-4.33) which was statistically significant in CACG patients. However, the odds of DD and NN genotypes against the reference genotype in two patients group were not statistically significant as compared to those of patients in the control group. There was a significant association between the ND genotype and male patients (OR = 2.28, 95% CI: 1.06-4.92). The analysis of TGF-ß1 (869T > C) polymorphisms showed no significant difference between the genotypes of TGF-ß1 (869T > C) polymorphisms in patients and control groups; however, the CT genotype of TGF-ß1 significantly differed between female controls and patients (OR = 0.42, 95% CI: 0.18-0.96). CONCLUSION: The presented results revealed that there was a significant association between the ND genotype of GSTO2 and the pathogenesis of glaucoma. Furthermore, this genotype can be considered as a sex-dependent genetic risk factor for the development of glaucoma. In contrast, the CT genotype of TGF-ß1 is suggested to be a protective genetic factor against the pathogenesis of glaucoma.

Effect of Electrical Stimulation on Ocular Cells: A Means for Improving Ocular Tissue Engineering and Treatments of Eye Diseases.

Tissue engineering is biomedical engineering that uses suitable biochemical and physicochemical factors to assemble functional constructs that restore or improve damaged tissues. Recently, cell therapies as a subset of tissue engineering have been very promising in the treatment of ocular diseases. One of the most important biophysical factors to make this happen is noninvasive electrical stimulation (ES) to target ocular cells that may preserve vision in multiple retinal and optic nerve diseases. The science of cellular and biophysical interactions is very exciting in regenerative medicine now. Although the exact effect of ES on cells is unknown, multiple mechanisms are considered to underlie the effects of ES, including increased production of neurotrophic agents, improved cell migration, and inhibition of proinflammatory cytokines and cellular apoptosis. In this review, we highlighted the effects of ES on ocular cells, especially on the corneal, retinal, and optic nerve cells. Initially, we summarized the current literature on the in vitro and in vivo effects of ES on ocular cells and then we provided the clinical studies describing the effect of ES on ocular complications. For each area, we used some of the most impactful articles to show the important concepts and results that advanced the state of these interactions. We conclude with reflections on emerging new areas and perspectives for future development in this field.

A Review on the Role of Stem Cells against SARS-CoV-2 in Children and Pregnant Women.

Since the COVID-19 outbreak was acknowledged by the WHO on 30 January 2020, much research has been conducted to unveil various features of the responsible SARS-CoV-2 virus. Different rates of contagion in adults, children, and pregnant women may guide us to understand the underlying infection conditions of COVID-19. In this study, we first provide a review of recent reports of COVID-19 clinical outcomes in children and pregnant women. We then suggest a mechanism that explains the curious case of COVID-19 in children/pregnant women. The unique stem cell molecular signature, as well as the very low expression of angiotensin-converting enzyme 2 and the lower ACE/ACE2 ratio in stem cells of children/pregnant women compared to adults might be the cause of milder symptoms of COVID-19 in them. This study provides the main molecular keys on how stem cells can function properly and exert their immunomodulatory and regenerative effects in COVID-19-infected children/pregnant women, while failing to replicate their role in adults. This can lay the groundwork for both predicting the pattern of spread and severity of the symptoms in a population and designing novel stem cell-based treatment and prevention strategies for COVID-19.

Mesenchymal Stem Cells and COVID-19: Cure, Prevention, and Vaccination.

COVID-19 disease has been a global health problem since late 2019. There are many concerns about the rapid spread of this disease, and yet, there is no approved treatment for COVID-19. Several biological interventions have been under study recently to investigate efficient treatment for this viral disease. Besides, many efforts have been made to find a safe way to prevent and vaccinate people against COVID-19 disease. In severe cases, patients suffer from acute respiratory distress syndrome usually associated with an increased level of inflammatory cytokines, called a cytokine storm. It seems that reequilibrating the hyperinflammatory response of the host immune system and regeneration of damaged cells could be the main way to manage the disease. Mesenchymal stem cells (MSCs) have been recently under investigation in this regard, and the achieved clinical outcomes show promising evidence for stem cell-based therapy of COVID-19. MSCs are known for their potential for immunomodulation, defense against virus infection, and tissue regeneration. MSCs are a newly emerged platform for designing vaccines and show promising evidence in this area. In the present study, we provided a thorough research study on the most recent clinical studies based on stem cells in the treatment of COVID-19 while introducing stem cell exclusivities for use as an immune disorder or lung cell therapy and its potential application for protection and vaccination against COVID-19.

Effects of the secretome of human Wharton's jelly mesenchymal stem cells on the proliferation and apoptosis gene expression of the retinal pigmented epithelium.

Human retinal pigmented epithelium (RPE) can undergo an uncontrolled proliferation in some disorders such as retinal detachment associated with proliferative vitreoretinopathy (PVR). The present study was conducted to evaluate the effect of the conditioned medium secreted by human Wharton's jelly mesenchymal stem cells (WJMSCs-CM) on the proliferation and apoptosis gene expression of the RPE. WJMSCs-CM was collected from WJMSCs after two periods of 24-h and 9-h culture in serum-free medium. RPE cells were cultured in WJMSCs-CM versus serum-deprived media for 24 h. The effect of WJMSCs-CM on RPE cell proliferation was determined using the MTT assay. Relative expression of apoptotic genes (Bcl2, Bax, and IL-1B) was also assessed by real-time PCR. MTT assay demonstrated that RPE cell viability was reduced significantly in WJMSCs-CM treated RPE cells compared to those cultured in serum-deprived medium (64.23 ± 2.44 vs 100.10 ± 5.68; P = 0.006). Moreover, the expression of anti-apoptotic Bcl2 was significantly decreased in WJMSCs-CM compared to serum-deprived medium (0.52 ± 0.06 in WJMSCs-CM vs 1.02 ± 0.2 in serum-free treatment; P = 0.03), while the expression of pro-apoptotic biomarkers of Bax and IL-1B was not significantly different between the two treatments. The represented data showed that WJMSCs-CM can induce apoptosis in RPE cells in vitro through activating apoptosis pathways. This proof-of-the-concept study provides basic evidence for the possible effect of WJMSCs-CM on preventing PVR.

Potential neuroprotective biomolecules in ophthalmology.

PURPOSES: Retinal neurodegenerative diseases are responsible for a huge number of ocular problems worldwide. It seems that the progression of these diseases can be managed by the application of neuroprotective molecules particularly in the early stages. This article focuses on the most common neuroprotective bioagents under investigation in ophthalmology. METHODS: We searched the web of science, PubMed and Scopus databases with these keywords: "glaucoma," "diabetic retinopathy," "age-related macular degeneration," "optic neuropathy and retinal degeneration" and/or "neuroprotection." RESULTS: The most commonly utilized neuroprotective drugs for ophthalmology diseases were introduced in this study. It seems that these agents can be divided into three categories according to their mechanism of action: (A) neurotrophins, (B) decreasing effect on intraocular pressure and (C) inhibition of retinal neuron apoptosis. CONCLUSION: A broad range of drugs has been illustrated in the literature for treatment of neuro-ophthalmic diseases. A good classification of the most applied drugs in this field can help specialists to prescribe the best matched drug considering the stage and progression of disease. However, controlled clinical trials are needed for better evaluation of the effects of these products.

The effects of intravitreal adalimumab injection on pseudophakic macular edema.

OBJECTIVE: Pseudophakic macular edema is a frequent complication following cataract surgery. Inflammation is a major etiologic factor in the development of pseudophakic cystoid macular edema. Tumor necrosis factor-alpha has an important role in ocular inflammation. Adalimumab (Humira) is an inhibitor of tumor necrosis factor-alpha that has been approved in the United States. An open-label, uncontrolled, prospective, interventional study of five consecutive patients (5 eyes) with cystoid macular edema who were treated with off-label intravitreal adalimumab at Khalili Hospital was conducted. Slit-lamp examination and optical coherence tomography were done for all patients. RESULTS: No statistically significant difference was detected between best corrected visual acuity and central macular thickness before and after injection in pseudophakic macular edema. One patient developed uveitis approximately 2 weeks after injection. Based on the results, adalimumab does not appear to be an effective treatment for pseudophakic macular edema, and it may cause uveitis. Caution should be exercised when using this drug. Trial registration Iranian Registry of Clinical Trials IRCT2016100430130N1, 2016.12.03, Retrospectively registered.