The adenosine A2A receptor antagonist KW6002 distinctly regulates retinal ganglion cell morphology during postnatal development and neonatal inflammation

Shisi Hu; Yaoyao Li; Yuanjie Zhang; Ruyi Shi; Ping Tang; Di Zhang; Xiuli Kuang; Jiangfan Chen; Jia Qu; Ying Gao

doi:10.3389/fphar.2022.1082997

The adenosine A_2A receptor antagonist KW6002 distinctly regulates retinal ganglion cell morphology during postnatal development and neonatal inflammation

Front Pharmacol. 2022 Dec 16:13:1082997. doi: 10.3389/fphar.2022.1082997. eCollection 2022.

Authors

Shisi Hu^{1

2

3

4}, Yaoyao Li^{1

2

3}, Yuanjie Zhang^{1

2

3}, Ruyi Shi^{1

2

3}, Ping Tang^{1

2

3}, Di Zhang^{1

2

3}, Xiuli Kuang^{1

2

3}, Jiangfan Chen^{1

2

3}, Jia Qu^{2

3}, Ying Gao^{1

2

3}

Affiliations

¹ The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China.
² State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China.
³ School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China.
⁴ Hainan Eye Hospital and Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Haikou, China.

Abstract

Adenosine A_2A receptors (A_2ARs) appear early in the retina during postnatal development, but the roles of the A_2ARs in the morphogenesis of distinct types of retinal ganglion cells (RGCs) during postnatal development and neonatal inflammatory response remain undetermined. As the RGCs are rather heterogeneous in morphology and functions in the retina, here we resorted to the Thy1-YFPH transgenic mice and three-dimensional (3D) neuron reconstruction to investigate how A_2ARs regulate the morphogenesis of three morphologically distinct types of RGCs (namely Type I, II, III) during postnatal development and neonatal inflammation. We found that the A_2AR antagonist KW6002 did not change the proportion of the three RGC types during retinal development, but exerted a bidirectional effect on dendritic complexity of Type I and III RGCs and cell type-specifically altered their morphologies with decreased dendrite density of Type I, decreased the dendritic field area of Type II and III, increased dendrite density of Type III RGCs. Moreover, under neonatal inflammation condition, KW6002 specifically increased the proportion of Type I RGCs with enhanced the dendrite surface area and volume and the proportion of Type II RGCs with enlarged the soma area and perimeter. Thus, A_2ARs exert distinct control of RGC morphologies to cell type-specifically fine-tune the RGC dendrites during normal development but to mainly suppress RGC soma and dendrite volume under neonatal inflammation.

Keywords: 3D reconstruction; adenosine A2A receptor; development; morphology; neonatal inflammation; retinal ganglion cell.