Erythropoietin (EPO) is a glycoprotein hormone conventionally thought to be responsible only in producing red blood cells in our body. However, with the discovery of the presence of EPO and EPO receptors in the retinal layers, the EPO seems to have physiological roles in the eye. In this review, we revisit the role of EPO in the eye. We look into the biological role of EPO in the development of the eye and the physiologic roles that it has. Apart from that, we seek to understand the mechanisms and pathways of EPO that contributes to the therapeutic and pathological conditions of the various ocular disorders such as diabetic retinopathy, retinopathy of prematurity, glaucoma, age-related macular degeneration, optic neuritis, and retinal detachment. With these understandings, we discuss the clinical applications of EPO for treatment of ocular disorders, modes of administration, EPO formulations, current clinical trials, and its future directions.

/pdf/revisiting-the-role-of-erythropoietin-for-treatment-of-arm4l2rnjw.pdf

Revisiting the role of erythropoietin for treatment of ocular disorders.

A study has shown that miR-423-5p is highly expressed in proliferative diabetic retinopathy. However, the exact biological functions and mechanisms of miR-423-5p in diabetic retinopathy (DR) progression are currently unclear. This study aimed to investigate the role of miR-423-5p in DR and the underlying mechanism. Our data demonstrate that the expression of miR-423-5p is significantly increased in HG-induced RPE cells and DR patient plasma. Moreover, the overexpression of miR-423-5p exacerbates HG-induced apoptosis. Mechanistically, our results provide evidence that miR-423-5p directly targets TFF1. MiR-423-5p exerts its effect on HG-induced apoptosis in RPE cells through TFF1, and the NF-κB pathway is involved in the regulatory mechanism. Further analysis revealed that the transcription factor NFE2 regulates miR-423-5p promoter activity. In addition, NFE2 regulates the levels of TFF1 and NF-κB pathway-associated proteins by regulating the expression of miR-423-5p. The NFE2-miR-423-5p-TFF1 axis is a novel molecular mechanism and provides a new direction for the study and treatment of DR.

/pdf/nfe2-mir-423-5p-tff1-axis-regulates-high-glucose-induced-pfob04aj7y.pdf

NFE2/miR-423-5p/TFF1 axis regulates high glucose-induced apoptosis in retinal pigment epithelial cells.

The efficacy of stem cell (SC) transplantation in patients with type 1 diabetes mellitus (T1DM) has remained to be fully elucidated In the present study, a systematic review and meta-analysis was performed to determine the clinical outcomes Electronic databases, including PubMed, MEDLINE, WanFang and the Cochrane Library were screened for relevant studies published until January 13, 2018 The references of retrieved papers, systematic reviews and trial registries were manually screened for additional papers Two authors were involved in screening the titles in order to select eligible studies, extract data and assess the risk of bias Studies were pooled using a random-effects model as well as the Begg's funnel plot and subgroup analysis was performed using Stata 140 software A total of 47 studies were retrieved for detailed evaluation, of which 22 met the inclusion criteria No substantial publication bias was identified The meta-analysis revealed that SC therapy increased C-peptide levels when compared with placebo treatment in randomized-controlled trials [RCT; standardized mean difference (SMD), 093; 95% confidence interval (CI) 023-163] and self-controlled trials (SMD, 066; 95% CI, -022 to 154) An analysis demonstrated that SC therapy was more efficient at reducing the glycated hemoglobin level compared with the control group in RCTs (SMD, 056; 95% CI; 006-106; and SMD, 163; 95% CI, 092-234, respectively) The graphs demonstrated that SC transplantation resulted in a reduction of insulin requirement Furthermore, subgroup analyses revealed that patient age, medical history and the SC injection dose may be sources of the heterogeneity observed The greatest benefit of SC transplantation was seen in patients aged ≥18 years or a medical history of <3 months In addition, the SC injection dose of ≥107 IU/kg/day was more effective than <107 IU/kg/day when the cellular composition included mesenchymal SCs and hematopoietic SCs In conclusion, SC therapy represents an efficient option for patients with T1DM This systematic review was registered at the International prospective register of systematic reviews (no 42018093930)

/pdf/stem-cell-transplantation-for-the-treatment-of-patients-with-9yh9y9xxd2.pdf

Stem cell transplantation for the treatment of patients with type 1 diabetes mellitus: A meta-analysis

Background and aims Diabetic kidney disease (DKD) is a major health issue that is associated with an increased risk of morbidity and mortality. The treatment of DKD is challenging given changes in blood glucose homeostasis, unclear accuracy of glucose metrics, and altered kinetics of the blood glucose-lowering medications. There is uncertainty surrounding the optimal glycemic target in this population although recent epidemiologic data suggest that HbA1c ranges of 6–8%, as well as 7–9%, are associated with increased survival rates among diabetic dialysis patients. Furthermore, the treatment of diabetes in patients maintained on dialysis is challenging, and many blood glucose-lowering medications are renally metabolized and excreted hence requiring dose adjustment or avoidance in dialysis patients. Method ology: PubMed, Google Scholar, and Medline were searched for all literature discussing the management of diabetes in dialysis patients. Results The literature was discussed under many subheadings providing the latest evidence in the treatment of diabetes in dialysis patients. Conclusion The management of diabetes in dialysis is very complex requiring a multi-disciplinary team involving endocrinologists and nephrologists to achieve targets and reduce morbidity and mortality.

Management of diabetes mellitus in dialysis patients: Obstacles and challenges

BACKGROUND Vitamin D (VD) deficiency and local inflammation of plaque are potential new risk factors and prevention goals for coronary heart disease (CHD). MATERIAL AND METHODS This study included 135 CHD patients and 45 chest tightness or chest pain patients (control group). Basic clinical data and serum 25-OH-VD, TNF-α, IL-6, IL-8, and IL-1β of the 2 groups were compared by SPSS 25.0. A CHD rat model was used to explore the potential molecular mechanisms. RESULTS The serum 25-OH-VD level in the control group was significantly higher compared to the CHD group, and decreased with the worsening of the CHD condition. Logistic regression found that serum 25-OH-VD was a protective factor in the occurrence of CHD. In CHD patients, the level of serum 25-OH-VD had a negative correlation with serum TNF-α (r=-0.651, P<0.001), IL-6 (r=-0.457, P<0.001), IL-8 (r=-0.755, P<0.001), and IL-1β (r=-0.628, P<0.001). In animal experiments, VD deficiency enhanced the level of serum TC, TG, and LDL-C. VD deficiency could increase the inflammatory response by upregulating the expression of p65 protein and reducing SIRT1 protein expression in heart tissue, thereby inducing or aggravating the state of CHD. CONCLUSIONS Serum 25-OH-VD was a protective factor in the occurrence of CHD, and VD deficiency could induce or aggravate the state of CHD by enhancing inflammation through the NF-κB pathway.

/pdf/vitamin-d-deficiency-harms-patients-with-coronary-heart-2xk0f58ksc.pdf

Vitamin D Deficiency Harms Patients with Coronary Heart Disease by Enhancing Inflammation.

Purpose: The purpose of this study was to evaluate whether any stage of diabetic retinopathy (DR) is associated with levels of plasma erythropoietin and other plasma parameters. Methods: It was examined a representative sample of 180 type 2 diabetes patients aged 40 to 79 years. Ophthalmic examination including a funduscopic examination, performed by an experienced ophthalmologist and the retinal finding were classified according to the grading system for diabetic retinopathy of ETDRS (Early Treatment Diabetic Retinopathy Study). It was measured the levels of plasma erythropoietin, cholesterol, triglyceride, apolipoproteins A and B, C-reactive protein, fasting blood glucose and hemoglobin A1C (HbA1C) in 88 DR patients and 92 controls without DR. Risk factors correlated with DR were compared between groups. Results: The study group of 180 patients included 72 males and 108 females. The mean age of the patients with and without DR was 57.36 ± 8.87 years and 55.33 ± 8.28 years, respectively. Of the 88 patients with DR, only 9 (10%) had proliferative DR and the rest suffered from non-proliferative DR. The mean plasma levels of erythropoietin in proliferative DR group showed a significant difference in comparison to other groups. The mean plasma levels of cholesterol, triglyceride, apolipoproteins A and B, C-reactive protein, and fasting blood glucose were not significantly different in the three groups except for HbA1C. The absolute relative risk (ARR) also showed that erythropoietin was an increasing risk for proliferative DR (ARR, 1.17; 95% confidence interval, 1.060 to 1.420; odds ratio,1.060). Conclusions: Of the factors studied, erythropoietin level showed significant increase in proliferative DR group. The stepwise raised in mean plasma erythropoietin level which demonstrates significant correlation with proliferative DR versus remaining two groups, will be an indication of its role in proliferative DR.

/pdf/diabetic-retinopathy-risk-factors-plasma-erythropoietin-as-a-c20how2wkl.pdf

Diabetic Retinopathy Risk Factors: Plasma Erythropoietin as a Risk Factor for Proliferative Diabetic Retinopathy

PURPOSE This study aims to determine the frequency of opthalmyomyiasis externa and the ocular findings of disease in Southern Khorasan. METHODS All patients referred to the emergency department of Valiaser hospital during the year 2011 with external ophthalmomyiasis were enrolled in this study. The diagnosis of external ophthalmomyiasis was made according to clinical findings and the presence of Oestrus ovis larvae. RESULTS There were 18 cases of external ophthalmomyiasis in the emergency department of Valiaser hospital in 2011. Most cases had the common signs and symptoms of allergic conjunctivitis, except for three males who were referred with respective complaints of red eye, foreign body sensation, and swelling around the eyelids after contact injury the previous day; corneal infiltration was present in three cases. The visual acuity among the three cases that had peripheral corneal involvement was 20 / 30 in both eyes. The bulbar conjunctiva showed chemosis in all cases and a ropy pattern discharge that was clinically compatible with external ophthalmomyiasis. However, in one case, microscopic slit lamp examination did not show Oestrus ovis larvae. CONCLUSIONS The frequency of external ophthalmomyiasis was high in this region. Although external ophthalmomyiasis usually manifests as allergic conjunctivitis, coronary-like corneal infiltration may be considered in the differential diagnosis of external ophthalmomyiasis or toxic insult.

/pdf/external-ophthalmomyiasis-presenting-to-an-emergency-18llegi61d.pdf

External Ophthalmomyiasis Presenting to an Emergency Department: Corneal Findings as a Sign of Oestrus ovis

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Diabetic Retinopathy Risk Factors: Plasma Erythropoietin as a Risk Factor for Proliferative Diabetic Retinopathy

External Ophthalmomyiasis Presenting to an Emergency Department: Corneal Findings as a Sign of Oestrus ovis