Amphiregulin and ocular axial length

Abstract

Purpose: To assess the potential role of amphiregulin as messenger molecule in ocular axial elongation. Methods: The experimental study included guinea pigs (total n = 78) (age: 3-4 weeks) which underwent bilateral lens-induced myopization and received 15 days later three intraocular injections in weekly intervals of amphiregulin antibody (doses:5 lg, 10 lg, 20 lg) into their right eyes, and three phosphatebuffered saline injections into their left eyes; and guinea pigs without lens-induced myopization and which received three unilateral intraocular injections of amphiregulin antibody (dose: 20 lg) or amphiregulin (doses: 1 ng; 10 ng; 20 ng) into their right eyes, and three phosphate-buffered saline injections into their left eyes. Seven days later, the animals were sacrificed. Intravitally, we performed biometry, and histology and immunohistochemistry post-mortem. Results: In animals with bilateral lens-induced myopization, the right eyes receiving amphiregulin antibody showed reduced axial elongation in a dose-dependent manner (dose: 5 lg: side difference: 0.14 AE 0.05 mm;10 lg: 0.22 AE 0.06 mm; 20 lg: 0.32 AE 0.06 mm; p < 0.001), thicker sclera (all p < 0.05) and higher cell density in the retinal nuclear layers and retinal pigment epithelium (RPE) (all p < 0.05). In animals without lens-induced myopia, the right eyes with amphiregulin antibody application (20 lg) showed reduced axial elongation (p = 0.04), and the right eyes with amphiregulin injections experienced increased (p = 0.02) axial elongation in a dosedependent manner (1 ng: 0.04 AE 0.06 mm; 10 ng: 0.10 AE 0.05 mm; 20 ng: 0.11 AE 0.06 mm). Eyes with lens-induced axial elongation as compared to eyes without lens-induced axial elongation revealed an increased visualization of amphiregulin upon immunohistochemistry and higher expression of mRNA of endogenous amphiregulin and epidermal growth factor receptor, in particular in the outer part of the retinal inner nuclear layer and in the RPE. Conclusion: Amphiregulin may be associated with axial elongation in young guinea pigs.

Ocular size and shape in lens-induced Myopization in young Guinea pigs

“…In one of these studies, the difference between eyes of young guinea pigs with goggles and those without goggles was 8.88 ± 0.08 mm (study group) and 8.67 ± 0.09 mm (control group) ( P = 0.002) [13]. In another investigation, the study and control group differed in axial length from 8.93 ± 0.06 mm to 8.76 ± 0.03 mm [26]. In guinea pigs with unilateral lens-induced axial elongation, axial length differed between both eyes from 8.93 ± 0.06 mm to 8.73 ± 0.03 mm [26].…”

“…In another investigation, the study and control group differed in axial length from 8.93 ± 0.06 mm to 8.76 ± 0.03 mm [26]. In guinea pigs with unilateral lens-induced axial elongation, axial length differed between both eyes from 8.93 ± 0.06 mm to 8.73 ± 0.03 mm [26]. A difference similar to the one found in our study was reported in a study by Xiao and colleagues in which guinea pigs with lens-induced myopization (7.89 ± 0.06 mm) and guinea pigs of a control group (7.75 ± 0.04 mm) differed in axial length by 0.14 mm [27].…”

Myopia: Anatomic Changes and Consequences for Its Etiology

“…It agreed with the findings obtained in aforementioned histomorphometric examination of human globes. 24,25 In another investigation conducted by Dong et al, 61 amphiregulin antibody applied intravitreally was associated with a reduction in lens-induced axial elongation and with a reduction of the physiological eye growth, whereas amphiregulin itself increased the axial elongation in young guinea pigs with and without lens-induced axial elongation. Eyes with lens-induced axial elongation as compared with eyes without lens-induced axial elongation revealed an increased visualization of amphiregulin upon immunohistochemistry and higher expression of mRNA of endogenous amphiregulin and epidermal growth factor (EGF) receptor, in particular in the outer part of the retinal inner nuclear layer and in the RPE.…”

“…Eyes with lens-induced axial elongation as compared with eyes without lens-induced axial elongation revealed an increased visualization of amphiregulin upon immunohistochemistry and higher expression of mRNA of endogenous amphiregulin and epidermal growth factor (EGF) receptor, in particular in the outer part of the retinal inner nuclear layer and in the RPE. 61 Amphiregulin is a member of the EGF family, and the RPE possesses receptors for EGF including amphiregulin. In particular, EGF increases the proliferation of RPE cells in cell culture.…”

Intraocular epidermal growth factor concentration, axial length, and high axial myopia

“…Experimental studies on chicken and guinea pigs revealed that various molecules if applied intraocularly or topically had an effect on an externally induced elongation of the optical axis. The list of these molecules includes dopamine and its agonists and antagonists, atropine, transforming growth factor beta (TGF-ß), fibroblast growth factor, hepatocyte growth factor, insulin-like growth factor, and amphiregulin, and other epidermal growth factor (EGF) family members [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. To further elucidate the potential association of EGF and its family members with the process of myopic axial elongation in humans, we undertook this study to examine the intraocular concentration of EGF in the aqueous humor of non-highly patients and patients with high myopia.…”