Intravitreal Stanniocalcin-1 Enhances New Blood Vessel Growth in a Rat Model of Laser-Induced Choroidal Neovascularization

Abstract

PurposeThe purpose of this study was to investigate the impact of stanniocalcin-1 (STC-1), a photoreceptor-protective glycoprotein, on the development of choroidal neovascularization (CNV) in relation to VEGF and its main receptor (VEGFR2) expression after laser injury.MethodsIn rats, CNV was induced by laser photocoagulation in both eyes, followed by intravitreal injection of STC-1 in the right eye and vehicle or denatured STC-1 injection in the left eye as control. Two weeks after laser injury, fundus autofluorescence (FAF) imaging and fundus fluorescein angiography (FFA) were performed. Fluorescein leakage from CNV was graded using a defined scale system. The size of CNV was quantified with spectral domain optical coherence tomography (SD-OCT), fluorescein-labeled choroid-sclera flat mounts, and hematoxylin-eosin staining. Protein expressions were evaluated by Western blot.ResultsPhotocoagulation produced a well-circumscribed area of CNV. With STC-1 treatment, CNV lesions assessed by FAF were increased by 50% in both intensity and area. The CNV lesions were also increased with SD-OCT, flat-mount, and histologic analyses. FFA disclosed enhanced fluorescein leakage in CNV lesions in STC-1 treated eyes. The STC-1 protein was detected in the choroidal tissue and its level was increased with CNV lesions in correlation with VEGF and VEGFR2 expressions. Intravitreal administration of STC-1 significantly increased choroidal expression of both VEGF and VEGFR2 proteins.ConclusionsChorodial tissue expresses STC-1, which seemingly acts as a stress response protein by enhancing pathological new blood vessel growth in laser-induced CNV. It is likely that STC-1 promotes CNV development via VEGF signaling.

Riboflavin deficiency leads to irreversible cellular changes in the RPE and disrupts retinal function through alterations in cellular metabolic homeostasis

“…6 C). In addition to hypoxia, angiogenic promoting genes, such as Stanniocalcin (Stc1) [ 46 , 47 ], are also upregulated in RDC-treated RPE ( Fig. 6 C).…”

Stanniocalcin-1 is a Modifier of Oxygen-Induced Retinopathy Severity

“…38 Paradoxically, STC-1 has been reported to induce VEGF signaling leading to increased angiogenesis in other model systems. [39][40][41] Additional studies in multiple cell types and disease models are needed to clarify the role of STC-1 in VEGF expression and signaling.…”

Dihydroartemisinin Inhibits Laser-Induced Choroidal Neovascularization in a Mouse Model of Neovascular AMD

“…For each CNV lesion, SD-OCT high-resolution multilinear horizontal scanning images were taken to calculate the thickness of the CNV lesion, which was defined as a spindleshaped hyperreflective area at the subretinal space. Only the scan that passed through the center of the lesion was chosen to evaluate the CNV central thickness (CCT) (Zhao et al, 2018).…”