Reduction of experimental ocular axial elongation by neuregulin-1 antibody

Xu Han Shi; Li Dong; Rui Heng Zhang; Wen Da Zhou; Yi Fan Li; Hao Tian Wu; He Yan Li; Chu Yao Yu; Yi Tong Li; Ya Xing Wang; Jost B Jonas; Wen Bin Wei

doi:10.3389/fmed.2023.1277180

Reduction of experimental ocular axial elongation by neuregulin-1 antibody

Front Med (Lausanne). 2023 Oct 26:10:1277180. doi: 10.3389/fmed.2023.1277180. eCollection 2023.

Authors

Xu Han Shi^{1

2

3}, Li Dong^{1

2

3}, Rui Heng Zhang^{1

2

3}, Wen Da Zhou^{1

2

3}, Yi Fan Li^{1

2

3}, Hao Tian Wu^{1

2

3}, He Yan Li^{1

2

3}, Chu Yao Yu^{1

2

3}, Yi Tong Li^{1

2

3}, Ya Xing Wang⁴, Jost B Jonas^{5

6}, Wen Bin Wei^{1

2

3}

Affiliations

¹ Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
² Beijing Ophthalmology and Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
³ Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
⁴ Beijing Ophthalmology and Visual Science Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Institute of Ophthalmology, Capital Medical University, Beijing, China.
⁵ Department of Ophthalmology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁶ Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.

Abstract

Background: Since the mechanisms underlying myopic axial elongation have remained unclear, we examined the effect of neuregulin-1 (NRG-1), an epidermal growth factor family member, on myopic axial elongation.

Methods: The guinea pigs aged two to three weeks were subjected to bilateral negative lens-induced axial elongation and received weekly intravitreal injections into their right eyes of NRG-1 antibody (doses: 5 μg, n = 8; 10 μg, n = 8, 20 μg, n = 9) or of NRG-1 (doses: 0.05 μg, n = 8; 0.01 μg, n = 9; 0.2 μg, n = 8), underwent only bilateral negative lens-induced axial elongation (myopia control group, n = 10), or underwent no intervention (control group, n = 10). The contralateral eyes received corresponding intravitreal phosphate-buffered solution injections. One week after the last injection, the guinea pigs were sacrificed, the eyeballs were removed, the thicknesses of the retina and sclera were histologically examined, the expression of NRG-1 and downstream signal transduction pathway members (ERK1/2 and PI3K/AKT) and the mRNA expression of NRG-1 in the retina was assessed.

Results: The inter-eye difference in axial length at study end increased (p < 0.001) from the normal control group (-0.02 ± 0.09 mm) and the myopia control group (-0.01 ± 0.09 mm) to the low-dose NRG-1 antibody group (-0.11 ± 0.05 mm), medium-dose NRG-1 antibody group (-0.17 ± 0.07 mm), and high-dose NRG-1 antibody group (-0.28 ± 0.06 mm). The relative expression of NRG-1, ERK1/2, and PI3K/AKT in the retina decreased in a dose-dependent manner from the myopia control group to the NRG-1 antibody groups and the normal control group. The relative NRG-1 mRNA expression in the retina was higher (p < 0.01) in the myopic control group than in the NRG-1 antibody groups and normal control group. Scleral and retinal thickness decreased from the normal control group to the NRG-1 antibody groups to the myopic control group. After intraocular injection of NRG-1 protein, there was a slight dose-dependent increase in the difference in axial length between the right and left eye, however not statistically significantly, from the normal control group (-0.02 ± 0.09 mm) to the high-dose NRG-1 protein group (0.03 ± 0.03 mm; p = 0.12).

Conclusion: Intravitreal NRG-1 antibody application was dose-dependently and time-dependently associated with a reduction in negative lens-induced axial elongation in young guinea pigs.

Keywords: EGF; axial elongation; epidermal growth factor; myopia; neuregulin-1.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by National Natural Science Foundation of China (82220108017 and 82141128), the Capital Health Research and Development of Special (2020-1-2052) and Science & Technology Project of Beijing Municipal Science & Technology Commission (Z201100005520045 and Z181100001818003).