Frontiers in Pharmacology (Dec 2022)
The adenosine A2A receptor antagonist KW6002 distinctly regulates retinal ganglion cell morphology during postnatal development and neonatal inflammation
- Shisi Hu,
- Shisi Hu,
- Shisi Hu,
- Shisi Hu,
- Yaoyao Li,
- Yaoyao Li,
- Yaoyao Li,
- Yuanjie Zhang,
- Yuanjie Zhang,
- Yuanjie Zhang,
- Ruyi Shi,
- Ruyi Shi,
- Ruyi Shi,
- Ping Tang,
- Ping Tang,
- Ping Tang,
- Di Zhang,
- Di Zhang,
- Di Zhang,
- Xiuli Kuang,
- Xiuli Kuang,
- Xiuli Kuang,
- Jiangfan Chen,
- Jiangfan Chen,
- Jiangfan Chen,
- Jia Qu,
- Jia Qu,
- Ying Gao,
- Ying Gao,
- Ying Gao
Affiliations
- Shisi Hu
- The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Shisi Hu
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Shisi Hu
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China
- Shisi Hu
- Hainan Eye Hospital and Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Haikou, China
- Yaoyao Li
- The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Yaoyao Li
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Yaoyao Li
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China
- Yuanjie Zhang
- The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Yuanjie Zhang
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Yuanjie Zhang
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China
- Ruyi Shi
- The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Ruyi Shi
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Ruyi Shi
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China
- Ping Tang
- The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Ping Tang
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Ping Tang
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China
- Di Zhang
- The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Di Zhang
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Di Zhang
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China
- Xiuli Kuang
- The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Xiuli Kuang
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Xiuli Kuang
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China
- Jiangfan Chen
- The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Jiangfan Chen
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Jiangfan Chen
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China
- Jia Qu
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Jia Qu
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China
- Ying Gao
- The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Ying Gao
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China
- Ying Gao
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China
- DOI
- https://doi.org/10.3389/fphar.2022.1082997
- Journal volume & issue
-
Vol. 13
Abstract
Adenosine A2A receptors (A2ARs) appear early in the retina during postnatal development, but the roles of the A2ARs 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 A2ARs 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 A2AR 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, A2ARs 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
- adenosine A2A receptor
- retinal ganglion cell
- morphology
- 3D reconstruction
- development
- neonatal inflammation
