Experimental eye research最新文献

Retinal vascular tortuosity presents valuable potential as a clinical biomarker for many relevant vascular and systemic diseases. Our work exhibits twofold: first, the definition of a novel scale-invariant metric to measure retinal blood vessel tortuosity; and second, the generation of a local database, called SCALE-TORT, with the intention of providing a means to test the scale invariance property on real retinal vessels rather than on synthetic data. The proposed scale invariant tortuosity metric is based on the Extended Slope Chain Code which uses variable straight-line segments for describing curves. It is focused on the representation of high-definition curves, the length of the segments is a function of the slope changes of the curve. Scale invariance is an important property when several different retinal image settings or different acquisition sources are used during a particular study or in clinical practice. The database SCALE-TORT, introduced herein, was built semi-automatically from digital images containing the coordinates of blood vessel central lines (curves) taken from images of the same eye obtained by two different imaging methodologies: retinal fundus camera and scanning laser ophthalmoscope. The vessel curves extracted from the same eye are paired for images acquired by the fundus camera and those acquired by the scanning laser ophthalmoscope to evaluate the scale invariance of the metric. Ten different tortuosity metrics were implemented and compared including our proposed metric. Three experiments were conducted to test the metrics and their properties. The first aimed to determine which tortuosity metrics possess the following properties: scale invariance, sensitivity to sudden tortuosity changes when the curve remains constant in size, and how they behave when curves are concatenated. In the second experiment, all reviewed metrics were tested on the publicly available RET-TORT database, to compare the results of the specific metric with the tortuosity classification provided by their experts and in comparison with other authors. Finally, in the third experiment, the behavior of different metrics, including those which are scale-invariant, were tested by utilizing the paired retinal vessel curves from our new SCALE-TORT database. In comparison with other tortuosity metrics, we show that the metric Extended Slope Chain Code proposed in this work optimally complies with scale invariance, in addition to having sufficient sensitivity to detect abrupt changes in tortuosity. Easy implementation being a further plus. Furthermore, we present a new and valueable database for scale property evaluation on images of retinal blood vessels called SCALE-TORT. As far as we are aware, there is no public database with these characteristics.

Age-related macular degeneration (AMD) is a complex, multifactorial retinal degenerative disease that is influenced by both genetic and environmental factors. However, the strongest risk factor for AMD is advanced age. Several physiological processes are observed in aging tissues including a low level of chronic inflammation (inflammaging), changed lipid and energy metabolism, and senescence. Nevertheless, whereas everyone ages, only a subset of the population develops AMD. The purpose of this review is to delineate the differences on a cellular and molecular level between natural aging changes and those observed in AMD. We provide a unique perspective on how genetic and environmental components modulate aging in the eye, as well as the specific role of the aging RPE and retina in the pathogenesis of AMD. Topics discussed include the mechanism of aging and its relation to the mechanism of AMD, current animal models that can be used to recapitulate some aspects of the pathology, and potential interventions that shift the balance towards healthy aging and therefore attenuate, prevent or delay the initiation of the disease.

In this study, we investigated the expression levels of miR-224-3p and inflammatory factors in the lens epithelium of patients with high myopia cataract (HMC) to determine how miR-224-3p/ACSL4 affects ferroptosis and inflammation in human lens epithelial cells (HLECs). The expression of miR-224-3p and ACSL4 in the capsules of patients was detected by qPCR, and RNA was extracted from each of the six capsules. To evaluate ferroptosis and inflammation, the level of expression of ACSL4, GPX4, and IL-6 was determined by immunohistochemistry, Transmission electron microscopy image showed the structure of mitochondria. The results of the PCR assays showed that the expression levels of miR-224-3p and IL-6 in the lens epithelium of HMC patients were significantly greater than those in ARC. ACSL4 and GPX4 in HMC were considerably lower than those in ARC. Electron microscopy images revealed that the mitochondria of HMC were significantly shrunken compared to those of ARC. A dual-luciferase report found miR-224-3p regulates ACSL4. PCR and WB assays revealed that ACSL4 was the downstream target gene of miR-224-3p. We also found that miR-224-3p promotes the proliferation and migration of HLECs. TNF-α (20 ng/mL) induced an inflammatory response in HLECs. Also, miR-224-3p effectively inhibited ferroptosis induced by erastin and decreased the level of expression of IL-6. Ferroptosis and inflammation occur in the eyes of HMC patients. Additionally, miR-224-3p increases the viability of HLECs by regulating ferroptosis and inflammation via ACSL4 targeting.

Retinitis pigmentosa (RP) is a genetic disorder often caused by single or multiple mutations. The progressive rod-cone degeneration (PRCD) gene is linked to retinal degeneration. This study identified a family affected by RP carrying a frameshift mutation (c.67del) in the PRCD gene. Blood samples from a patient with RP and three family members were analyzed by whole-exome sequencing. A point-mutant mouse model was created using gene-targeted modification to validate the suspected causative gene phenotypically. Binocular ophthalmological exams, including electroretinography and optical coherence tomography (OCT), were performed at P0, P30, P60, and P180. After 180 days, retinas were analyzed by polymerase chain reaction (PCR) , Western blotting (WB) and immunofluorescence to measure gene expression and observe phenotypical changes, respectively. We used whole-exome sequencing of peripheral blood to identify a novel frameshift mutation in the PRCD gene: c.67del (p.Val23SerfsTer31). This mutation introduces a premature termination codon at amino acid position 31. Predictive tools indicate that this mutation is likely pathogenic. The proband's parents are consanguineous; the mother is a heterozygous carrier; the remaining two living family members exhibit a wild-type genotype. PCR, WB and immunofluorescent staining revealed significantly low Prcd expression in the Prcd^-/- mice than in wild-type mice. OCT and visual electrophysiological assessments detected lesions in the fundus of Prcd^-/- mice eyes; the severity of pathological changes increased with age. This study discovered a new mutation in the RP-associated Prcd gene and confirmed that it causes retinopathy in Prcd^-/- mice.