Inhibitory effect of miR­182­5p on retinal neovascularization by targeting angiogenin and BDNF.

Retinal neovascularization (RNV) is a type of serious vision­threating disease, commonly induced by hypoxia of ischemic retinopathy, which happens in various ocular diseases including diabetic retinopathy and retinopathy of prematurity. In clinical work, anti­VEGF therapy is the preferred strategy for treating RNV. However, not all cases are sensitive to anti­VEGF injection. It is urgent and necessary to develop novel targets for inhibiting neovascularization in ocular diseases. Angiogenin (ANG) and brain­derived neurotrophic factor (BDNF) are implicated in angiogenesis, although their regulation and effects in RNV remain to be elucidated. microRNA (miRNA) is a type of small non­coding RNA, which can modulate targets by degrading transcripts or inhibiting protein translation. In the present study, miRNA­mediated modulation of ANG and BDNF was explored in an oxygen­induced retinopathy mouse model and human retinal microvascular endothelial cells (HRECs) under hypoxia. The results showed that downregulation of miR­182­5p and upregulation of ANG and BDNF were found in vivo and in vitro. Overexpression of miR­182­5p suppressed the expression of ANG and BDNF significantly in HRECs under hypoxia. In addition, knockdown of ANG and BDNF by miR­182­5p transfection significantly improved hypoxia­induced HRECs dysfunctions, including enhancing cell viability, reducing cell migration and improved tube integrity. In conclusion, miRNA­dependent regulation on ANG and BDNF indicates a critical role in hypoxia­induced retinal microvascular response. miR­182­5p­based therapy can influence the expression of ANG and BDNF, which demonstrates the potential for treating RNV diseases.

Comparative Study of a Modified Sub-Tenon's Capsule Injection of Triamcinolone Acetonide and the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Retinitis Pigmentosa Combined With Macular Edema.

Retinitis pigmentosa (RP) is a hereditary retinal degenerative disease leading to eventual blindness. When RP is combined with macular edema (ME), the visual impairment further worsens. We compared a modified sub-Tenon's capsule injection of triamcinolone acetonide (TA) and the intravenous infusion of umbilical cord mesenchymal stem cells (UCMSCs) in the treatment of RP combined with ME (RP-ME) to assess their safety and efficacy in eliminating ME and restoring visual function. A phase I/II clinical trial enrolled 20 patients was conducted. All patients were followed up for 6 months. There were no severe adverse effects in both groups. In retinal morphological tests, the central macular thickness (CMT) in TA group significantly decreased at first week, first and second month after injection (p < 0.05). The CMT in UCMSCs group significantly decreased at first month after infusion. The rate of reduction of CMT in TA group was significantly greater than that in UCMSCs group at second month (p < 0.05). Reversely, the rate of reduction of CMT in UCMSCs group was significantly greater than that in TA group at sixth month (p < 0.05). In visual functional test, although there were no significant differences in visual acuity or visual fields within each group or between groups, but the amplitude of P2 wave of flash visual evoked potential (FVEP) showed significant increasing in TA group at second month in UCMSCs group at sixth month (p < 0.05). At 6th month, the rate of growth in the amplitude of P2 wave in USMCSs group was significantly greater than that in TA group (p < 0.05). This study suggests both modified sub-Tenon's capsule injection of TA and intravenous infusion of UCMSCs are safe for RP-ME patients. TA injection is more effective at alleviating ME while improving visual function in a short term. UCMSC intravenous infusion shows slow but persistent action in alleviating ME, and can improve the visual function for a longer time. These approaches can be applied separately or jointly depending on the disease condition for patients to benefit maximumly. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR-ONC-16008839.

Long-term follow-up of a Chinese patient with KCNV2-retinopathy.

Purpose: To characterize and monitor the clinical and electrophysiological features of a Chinese patient with KCNV2 retinopathy.Methods: A 17-year-old Chinese male with the diagnosis of cone dystrophy with supernormal rod response (CDSRR) was followed-up for 5 years, with full ophthalmological examinations, including decimal best corrected visual acuity (BCVA), fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography (SD-OCT), and full-field electroretinogram (ERG). Genetic screening was performed to detect the sequence variations in the retinal dystrophy associated genes in the patient and his parents.Results: The patient demonstrated the characteristic full-field electroretinography (ERG) features of CDSRR, namely a profound enlargement of the dark-adapted ERG b-wave amplitude with increasing flash strength and a broadened a-wave trough; this case also had undetectable light-adapted ERGs. A BCVA of 0.15 was maintained over 5 years in both eyes; while progressive macular atrophy was identified. Molecular genetic analyses revealed two novel disease-causing KCNV2 variants in compound heterozygous state: c.1408 G > C (p.Gly470Arg) and c.1500 C > G (p.Tyr500Ter).Conclusions: This is the first long-term case study of an East Asian patient with molecularly confirmed CDSRR. The progressive atrophy with maintained VA demonstrated in this case will be valuable for increasing the understanding of the natural course of KCNV2 retinopathy and it will help in counselling patients with this disease.

Fish oil supplementation and repeated macular hemorrhage without choroidal neovascularization: A case report.

Macular hemorrhage can occur spontaneously and repeatedly without choroidal neovascularization or other known lesions associated with myopia. We report a case of repeated myopic macular hemorrhage following fish oil supplementation. A 32-year-old male was referred with newly acquired paracentral scotoma in the left eye. Serial retinal imaging, including fundus photography, fluorescein angiography, and spectral-domain optical coherence tomography were performed. Fundus photography and fluorescein angiography showed a subtle red-colored lesion nasal to the fovea. Optical coherence tomography showed a dome shaped elevation in the ellipsoid zone and interdigitation zone in the left eye. No known ocular risk factors for macular hemorrhage, such as choroidal neovascularization, lacquer cracks, Fuch's spot or choroid thinning or keratoconus were observed. After 2 months without any treatment, the left eye lesion disappeared. However 2 weeks later, another newly developed red-colored lesion close to the left fovea was observed. At that moment, the detailed medical history revealed that the patient had been regularly taking a high dose of commercially available fish oil supplement beginning one month before the first macular hemorrhage. After discontinuation of the fish oil, the second left hemorrhage resolved gradually over the following 8 weeks. No recurrent hemorrhages have been detected at the 12 months follow-up visits. Our observations suggest that the relative value of nutritional supplementation with high doses of fish oil should be cautioned in patients with repetitive retinal hemorrhage.