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Inherited retinal diseases (IRDs) can induce severe sight-threatening retinal degeneration and impose a considerable economic burden on patients and society, making efforts to cure blindness imperative. Transgenic animals mimicking human genetic diseases have long been used as a primary research tool to decipher the underlying pathogenesis, but there are still some obvious limitations. As an alternative strategy, patient-derived induced pluripotent stem cells (iPSCs), particularly three-dimensional (3D) organoid technology, are considered a promising platform for modeling different forms of IRDs, including retinitis pigmentosa, Leber congenital amaurosis, X-linked recessive retinoschisis, Batten disease, achromatopsia, and best vitelliform macular dystrophy. Here, this paper focuses on the status of patient-derived iPSCs and organoids in IRDs in recent years concerning disease modeling and therapeutic exploration, along with potential challenges for translating laboratory research to clinical application. Finally, the importance of human iPSCs and organoids in combination with emerging technologies such as multi-omics integration analysis, 3D bioprinting, or microfluidic chip platform are highlighted. Patient-derived retinal organoids may be a preferred choice for more accurately uncovering the mechanisms of human retinal diseases and will contribute to clinical practice.

Background X-linked juvenile retinoschisis (XLRS) is an inherited disease caused by RS1 gene mutation, which leads to retinal splitting and visual impairment. The mechanism of RS1 -associated retinal degeneration is not fully understood. Besides, animal models of XLRS have limitations in the study of XLRS. Here, we used human induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs) to investigate the disease mechanisms and potential treatments for XLRS. Methods hiPSCs reprogrammed from peripheral blood mononuclear cells of two RS1 mutant (E72K) XLRS patients were differentiated into ROs. Subsequently, we explored whether RS1 mutation could affect RO development and explore the effectiveness of RS1 gene augmentation therapy. Results ROs derived from RS1 (E72K) mutation hiPSCs exhibited a developmental delay in the photoreceptor, retinoschisin (RS1) deficiency, and altered spontaneous activity compared with control ROs. Furthermore, the delays in development were associated with decreased expression of rod-specific precursor markers (NRL) and photoreceptor-specific markers (RCVRN). Adeno-associated virus (AAV)-mediated gene augmentation with RS1 at the photoreceptor immature stage rescued the rod photoreceptor developmental delay in ROs with the RS1 (E72K) mutation. Conclusions The RS1 (E72K) mutation results in the photoreceptor development delay in ROs and can be partially rescued by the RS1 gene augmentation therapy.

Spherical culture could promote the plasticity and stemness of human corneal stromal cells (hCSCs). Here, we introduce a novel three-dimensional (3D) cell culture system based on a polydimethylsiloxane (PDMS) microwell platform composed of many V-bottom microcavities to generate human corneal stromal cell spheroids and promote cell stemness. We isolated hCSCs from SMILE-derived lenticules and maintained their physiological phenotype by culturing them in a medium supplemented with human corneal stromal extract (hCSE). Utilizing a PDMS microwell platform fabricated through 3D printing technology, we successfully generated 3D corneal stromal cell spheroids (3D-CSC) with uniform size and stable structure, exhibiting increased expression of pluripotency factors, including OCT4, NANOG, SOX2, KLF4, and PAX6. Furthermore, the iPS supernatant of E8-conditioned medium (E8-CM) significantly enhanced the stemness properties of these cells. RNA sequencing and proteomics analyses revealed that 3D-CSCs exhibited superior proliferation, differentiation, cell adhesion, migration, and neurogenesis compared to traditional monolayer cultures, underscoring the role of biophysical cues in promoting hCSCs stemness. In summary, this study presents an effective 3D cell culture platform that mimics the in vivo microenvironment, facilitating the enhancement of stemness properties and providing valuable insights into corneal tissue engineering and regenerative medicine, particularly for treating corneal opacities and diseases.

To study the factors protecting against diabetic retinopathy (DR) in patients with over a decade-long history of type 2 diabetes mellitus. A total of 490 patients with type 2 diabetes mellitus lasting for ≥10 years were divided into DR and no diabetic retinopathy (no DR) groups. Their basic information was collected, including age, sex, and duration of diabetes mellitus, as well as pertinent laboratory data. Potential correlations between these factors and DR were evaluated using multivariate analysis. Overall, 208 patients met the diagnostic criteria for DR. Multivariate logistic regression was used to evaluate factors with P < 0.10 after univariate analysis. Age, total bilirubin, and total cholesterol were found to be protective factors against DR. Presence of diabetic kidney disease and diabetic peripheral neuropathy, duration of diabetes mellitus, apolipoprotein B, blood urea nitrogen, and prothrombin time were found to be risk factors for DR. We conclude that total cholesterol is a protective factor against DR. Specifically, it was confirmed that high levels of total cholesterol reduce the risk of DR. These findings may provide a basis for new diet and lifestyle guidelines for patients with diabetes mellitus.

Purpose To compare the effect of bilateral inferior oblique partial myectomy on V-pattern exotropia patients with bilateral symmetric inferior oblique overaction (IOOA) and asymmetric IOOA. Methods This was a retrospective study including 53 V-pattern exotropia patients with bilateral IOOA of all grades who underwent bilateral inferior oblique partial myectomy. Success was defined as the elimination of the IOOA and the collapse of the V pattern at the final follow-up. The fovea-disc angle (FDA) and V-pattern exotropia were compared before and after surgery. Results This study included 53 V-pattern exotropia patients, containing 29 patients with symmetric IOOA (Group I) and 24 patients with asymmetric IOOA (Group II). The last follow-up ranged from 3 to 16 months (mean of 5 months). After myectomy, 3 eyes in Group I and 2 eyes in Group II were observed with residual grade 1 IOOA. The surgical success rates of IOOA correction in Group I and Group II were 96% and 95%, respectively. The difference was not statistically significant ( P  = 0.808). V-pattern exotropia collapsed with residual 2 (min. 0, max. 6) PD for Group I and 2 (min. 0, max. 10) PD for Group II, and there was a statistically significant difference between pre- and postoperative V-pattern exotropia in the two groups ( P  = 0.000). No inferior oblique (IO) underaction or antielevation syndrome (AES) was found in either group. The average preoperative FDA of the right eye and the left eye was (8.93 ± 4.34)° and (10.86 ± 4.27)° in Group I and (9.08 ± 4.92)° and (11.00 ± 5.69)° in Group II. There was a significant difference in preoperative FDA between the right eye and the left eye in the two groups (Group I p  = 0.029; Group II p  = 0.038). Conclusions Bilateral inferior oblique partial myectomy can bring “symmetric” effectiveness in the correction of IOOA and FDA. It can potentially be used as a safe and successful treatment for V-pattern exotropia with bilateral IOOA. In addition, the FDA may be a promising index for evaluating fundus extorsion.

EpCAM is expressed at low levels in a variety of normal human epithelial tissues, but is overexpressed in 70-90% of carcinomas. From a clinico-pathological point of view, this has both prognostic and therapeutic significance. EpCAM was first suggested as a therapeutic target for the treatment of epithelial cancers in the 1990s. However, following several immunotherapy trials, the results have been mixed. It has been suggested that this is due, at least in part, to an unknown level of EpCAM expression in the tumors being targeted. Thus, selection of patients who would benefit from EpCAM immunotherapy by determining EpCAM status in the tumor biopsies is currently undergoing vigorous evaluation. However, current EpCAM antibodies are not robust enough to be able to detect EpCAM expression in all pathological tissues. Here we report a newly developed EpCAM RNA aptamer, also known as a chemical antibody, which is not only specific but also more sensitive than current antibodies for the detection of EpCAM in formalin-fixed paraffin-embedded primary breast cancers. This new aptamer, together with our previously described aptamer, showed no non-specific staining or cross-reactivity with tissues that do not express EpCAM. They were able to reliably detect target proteins in breast cancer xenograft where an anti-EpCAM antibody (323/A3) showed limited or no reactivity. Our results demonstrated a more robust detection of EpCAM using RNA aptamers over antibodies in clinical samples with chromogenic staining. This shows the potential of aptamers in the future of histopathological diagnosis and as a tool to guide targeted immunotherapy.