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Retinitis punctata albescens (RPA) is generally diagnosed by the presence of numerous clusters of white punctate lesions in the retina that progress over time and are related to several gene variants. The multifocal variant of congenital hypertrophy of the retinal pigment epithelium (CHRPE) is characterized by multiple, grouped, sharply circumscribed, pigmented spots. The PRPH2gene encodes a photoreceptor-specific glycoprotein, which is essential for the morphogenesis of rod and cone photoreceptor outer segments. A 39-year-old Chinese female with nyctalopia, complained about blurred vision, presented a unique co-existing feature of RPA and CHRPE. Dilated fundus exam demonstrated numerous porcelain white discrete dots in both eyes and multiple, small, flat clusters of round brown to black pigmented lesions in the left eye. The full field electroretinography (ERG) showed decreased responses after standard dark adaptation and normal b-wave amplitudes after a long (4-h) dark-adapted period. A heterozygous PRPH2splicing variant was detected in the proband. In addition, the same variant was found in her mother, her son, and her daughter. We describe a PRPH2variant in a rare case of RPA associated with multifocal CHRPE of the same individual.

Retinal pigment epithelial (RPE) cell replacement therapy has provided promising outcomes in the treatment of retinal degenerative diseases (RDDs), but the resulting limited visual improvement has raised questions about graft survival and differentiation. Through combined treatment with vitamin C and valproic acid (together, VV), we activated human fetal RPE (fRPE) cells to become highly proliferative fetal RPE stem-like cells (fRPESCs). In this study, we report that SOX2 (SRY-box 2) activation contributed to mesenchymal-epithelial transition and elevated the retinal progenitor and mesenchymal stromal markers expressions of fRPESCs. These fRPESCs could differentiate into RPE cells, rod photoreceptors, and mesenchymal lineage progenies under defined conditions. Finally, fRPESCs were transplanted into the subretinal space of an RDD mouse model, and a photoreceptor rescue benefit was demonstrated. The RPE and rod photoreceptor differentiation of transplanted fRPESCs may account for the neural retinal recovery. This study establishes fRPESCs as a highly proliferative, multi-lineage differentiation potential (including RPE, rod photoreceptor, and mesenchymal lineage differentiation), mesenchymal-to-epithelial-transitioned retinal stem-like cell source for cell-based therapy of RDDs.

Objective: To investigate the potential correlation between complement factor B polymorphisms and age-related macular degeneration.Methods: We retrieved relevant articles systematically by searching PubMed and Web of Science databases. The pooled odds ratios and 95% confidence intervals were calculated for five complement factor B polymorphism rs641153, rs4151667, rs1048709, rs2072633, and rs12614 using data from included articles in both random effects and fixed effect models. Subgroup meta-analysis based on age-related macular degeneration type, choroidal neovascular disease (rs641153 and rs4151667), geographic atrophy (rs641153 and rs4151667), and races was also performed.Results: In the overall comparison, we observed that the distribution of rs641153 and the risk of age-related macular degeneration were significantly correlated (p < 0.00001). Similar results were obtained in subgroup analysis based on race (Caucasians, p < 0.00001; Asians, p = 0.003) and age-related macular degeneration type (choroidal neovascular disease, p < 0.00001; geographic atrophy, p = 0.04). As for complement factor B rs4151667, the genotypic effects were also demonstrated statistically significant in overall analysis (p < 0.00001) and only in Caucasians diagnosed with choroidal neovascular disease (p = 0.004), but not in Asians. Moreover, no statistically significant correlations between the complement factor B polymorphisms rs1048709 (p = 0.63), rs2072633 (p = 0.72), rs12614 (p = 0.98) and susceptibility to age-related macular degeneration were detected in either overall or subgroup analysis.Conclusion: Collectively, we demonstrated that the complement factor B genes rs641153 and rs4151667, but not rs1048709, rs2072633, rs12614, were associated with the susceptibility of age-related macular degeneration and might play predictive roles in future age-related macular degeneration diagnosis. More studies are needed to verify these findings.

Age-related macular degeneration (AMD) is a universal leading cause for irreversible blindness in the elderly population. Dedifferentiation of retinal pigment epithelium (RPE) cells initiates early pathological events in atrophic AMD. Herein, we aim to investigate effects of a circular RNA derived from the NR3C1gene (circNR3C1) on regulating RPE function and AMD pathogenesis. circNR3C1 expression was consistently upregulated along with RPE differentiation and was downregulated in dysfunctional RPE and blood serum of AMD patients. Silencing of circNR3C1 reduced RPE characteristic transcripts and proteins, interrupted phagocytosis, accelerated intracellular reactive oxygen species (ROS) generation, and promoted RPE proliferation in vitro. circN3C1 silencing also decreased expressions of RPE characteristic markers and disturbed the ultrastructure of RPE in vivo, as shown by a thickened RPE with twisted basal infoldings and outer segments. Mechanistically, circNR3C1 acted as an endogenous microRNA-382-5p (miR-382-5p) sponge to sequester its activity, which increased phosphatase and tensin homolog on chromosome 10 (PTEN) expression and inhibited the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway. miR-382-5p overexpression and PTEN silencing mimicked effects of circNR3C1 silencing on RPE phenotypes in vivoand in vitro. In conclusion, circNR3C1 prevents AMD progression and protects RPE by directly sponging miR-382-5p to block its interaction with PTENand subsequently blocks the AKT/mTOR pathway. Pharmacological circNR3C1 supplementations are promising therapeutic options for atrophic AMD.

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A 36-year-old man was diagnosed with Schwartz-Matsuo syndrome and received a scleral buckle surgery. Photoreceptor outer segments in aqueous humor were examined under electron microscope to confirm the diagnosis. Afterwards, 17 human angiogenesis and growth factor biomarkers were chosen to make simultaneous quantification in aqueous humor, among which the authors demonstrated the remarkable high expression of angiopoietin-2 in aqueous humor. This is the first reported case of angiogenesis / growth factor biomarkers in aqueous humor of the Schwartz-Matsuo Syndrome patient. Angiopoietin-2 level significantly increased in this patient's aqueous humor, which helped the authors to illuminate the pathogenic mechanisms underlying Schwartz-Matsuo syndrome.[[Ophthalmic Surg Lasers Imaging Retina. 2018;49:721–725.]

The purpose of this study is to investigate the effectiveness of a new surgical technique of non-inverted pedicle internal limiting membrane (ILM) transposition for the treatment of eyes with large macular hole. This is a retrospective, consecutive, interventional case series. Twelve eyes of 12 consecutive patients who underwent vitrectomy for the treatment of a large macular hole (MH size > 400 µm) were treated. ILM was peeled and left with a pedicle attached to the superior temporal retina. The macular hole was covered by transposition of the pedicle ILM in a non-inverted way. Preoperative and postoperative best-corrected visual acuity (BCVA), SD-OCT image, macular sensitivity by microperimetry, and multifocal electroretinogram (mERG) response were evaluated. All of the patients were followed for more than 3 months. Postoperative OCT examination confirmed 11 of 12 macular hole closed (91.7%). Six macular hole filled with silicone oil closed as early as the next day. The postoperative BCVA significantly increased compared with preoperative BCVA (P= 0.002). The improvement of macular sensitivity within 2° and 8° circle was also statistical significant (P= 0.018 and P= 0.017, respectively). Fixation stability, shown as the percentage of fixation point within the 2° circle and 4° circle, was remarkably improved (P= 0.017 and P= 0.018, respectively). The R1/R2 and R1/R4 ring ratios also increased significantly as compared with that of baseline. These findings indicate that the non-inverted pedicle ILM transposition results in a high incidence of anatomic closure with good visual outcome for the treatment of large macular hole.

PurposeTo evaluate the efficacy of oral spironolactone in patients with acute central serous chorioretinopathy (CSC).MethodsThis is a prospective, randomised controlled clinical study. Thirty patients with acute CSC were the participants, including 18 patients who were treated with spironolactone (40 mg orally, twice daily) for 2 months in the experimental group and 12 patients who received observation in the control group. Main outcome measures included the proportion of eyes achieving complete resolution of subretinal fluid (SRF), changes in central macular thickness (CMT), the height of SRF (SRFH), best corrected visual acuity (BCVA) and subfoveal choroidal thickness (SFCT). The follow-up period was 2 months.ResultsComplete resolution of SRF was achieved in 55.6% (10/18) and 8.3% (1/12) of the eyes in the treatment group and the control group, respectively, at 2 months (p=0.018). The mean CMT and SRFH decreased significantly at each visit in both groups (p<0.05), and there was significant difference between the two groups at 2 months (p<0.05 and p<0.05, respectively). BCVA (in logarithm of the minimum angle of resolution; mean) improved in both groups at 2 months (p<0.05). In the treatment group, the mean baseline SFCT significantly decreased from 502.50±87.38 µm to 427.44±74.37 µm at 2 months (p<0.01), while the change from baseline (from 480.33±102.38 µm to 463.75±100.63 µm) was not significant in the control group (p=0.195). But the differences between the two groups in BCVA and SFCT were not significant.ConclusionsOral spironolactone is more effective with a faster absorption of SRF than observations. It is a promising treatment for acute CSC.Trial registration numberChiCTR-IPR-16008428, Results.

ObjectiveThe aim of this review is to determine whether vitreomacular adhesion (VMA) or vitreomacular traction (VMT) has an influence on the outcomes of antivascular endothelium growth factor (anti-VEGF) treatment neovascular age-related macular degeneration (nAMD).MethodsA systematic literature search was performed in Pubmed.gov, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, SinoMed and ClinicalTrials.gov up to 30 June 2016 to identify eligible studies.ResultsNine studies and 2212 participants were finally identified. At month 6, the mean improvement in best-corrected visual acuity (BCVA) and mean decline in central retinal thickness (CRT) of the VMA/VMT(+) group was less than that of the VMA/VMT(-) group (95% CI −3.05 to –0.96 letters, p=0.0002; 15.53 to 32.98 μm, p<0.00001; respectively); at month 12, there was a small or only marginally significant difference (−0.01 to 2.00 letters, p=0.05; 0.17 to 23.7 μm, p=0.05; respectively) between the groups. During the 12 months, however, the VMA/VMT(+) group required more injections ((0.25 to 0.95), p=0.0008).ConclusionsIn using anti-VEGF drugs to treat nAMD, clinicians should take into account the fact that concurrent VMA or VMT might antagonise the efficacy of anti-VEGF drugs during the early stage of treatment.

Retinal development is initiated by multipotent retinal progenitor cells, which undergo several rounds of cell divisions and subsequently terminal differentiation. Retinal regeneration is usually considered as the recapitulation of retinal development, which share common mechanisms underlying the cell cycle re-entry of adult retinal stem cells and the differentiation of retinal neurons. However, how proliferative retinal progenitor cells perform a precise transition to postmitotic retinal cell types during the process of development and regeneration remains elusive. It is proposed that both the intrinsic and extrinsic programming are involved in the transcriptional regulation of the spatio-temporal fate commitment. Epigenetic modifications and the regulatory mechanisms at both DNA and chromatin levels are also postulated to play an important role in the timing of differentiation of specific retinal cells. In the present review, we have summarized recent knowledge of epigenetic regulation that underlies the commitment of retinal progenitor cells in the settings of retinal development and regeneration.

By hybridizing human adult testis cDNA microarrays with human adult and embryo testis cDNA probes, we identified a novel human testis gene, NYD-SP15. NYD-SP15 expression was 3.26-fold higher in adult than in fetal testis; however, there was almost no NYD-SP15 expression in the sperm. NYD-SP15 comprises 3364 base pairs, including a 1545 bp open reading frame encoding a 514 amino acid protein possessing 89% sequence identity with the mouse testis homologous protein. NYD-SP15 is located on human chromosome 13q14.2. The deduced structure of the protein contains two dCMP_cyt_deam domains, indicating a potential functional role for zinc ion binding. The gene is expressed variably in a wide range of tissues, with high expression levels in the testis. Sequence analysis revealed that NYD-SP15 is not a highly conserved protein, with its distribution in high-level species such as vertebrates including Homo, Mus, Rattus, and Canis. The results of semiquantitative polymerase chain reaction in mouse testis representing different developmental stages indicate that NYD-SP15 expression was developmentally regulated. These results suggest the putative NYD-SP15 protein may play an important role in testicular development and spermatogenesis and may be an important factor governing male infertility.