TY - JOUR
T1 - Changes in Starburst Amacrine Cells in Mice with Diabetic Retinopathy
AU - Son, Jae Rim
AU - Lee, Myung Jun
AU - Jeon, Chang Jin
N1 - Publisher Copyright:
© 2023 The Author(s). Published by IMR Press. This is an open access article under the CC BY 4.0 license.
PY - 2023/5
Y1 - 2023/5
N2 - Background: Neurodegenerative diseases, such as diabetic retinopathy (DR) and glaucoma, induce retinal neuron loss. Acetylcholinecontaining cholinergic neurons, known as starburst amacrine cells (SACs), play critical roles in the generation of precise neuronal activity in the retina and are located in the inner nuclear layer (INL, conventional) and ganglion cell layer (GCL, displaced). Methods: This study investigated the loss of and morphological changes in SACs in the retinas of streptozotocin (STZ)-induced diabetic and insulin-deficient C57BL/6-Tg(pH1-siRNAinsulin/CMV-hIDE)/Korl (IDCK) mice. SACs were immunocytochemically localized with anti-choline acetyltransferase (ChAT) antibody, and ChAT-labeled cells in the INL and GCL in the control and experimental groups were counted along the central vertical meridian in the whole-mounted retina using conventional fluorescent or confocal microscopes. Results: ChAT-immunoreactive (IR) neurons in STZ-induced diabetic mouse retina decreased by 8.34% at 4-6 weeks and by 14.89% at 42 weeks compared with the control group. Localized ChAT-IR neuron counts in the retinas of 20-week-old IDCK mice were 16.80% lower than those of age-matched control mice. Cell body deformation and aggregation were detected in the retinas of mice with DR. Single-cell injection experiments revealed the loss and deformation of dendritic branches in ChAT-IR neurons in DR. All ChAT-IR neurons expressed the calcium-binding protein calretinin, whereas no ChAT-IR neuron colocalized with calbindin-D28K or parvalbumin. Conclusions: Our results revealed that the neurodegenerative effects of the loss and deformation of ChAT-IR neurons can provide a reference for future study of this disease.
AB - Background: Neurodegenerative diseases, such as diabetic retinopathy (DR) and glaucoma, induce retinal neuron loss. Acetylcholinecontaining cholinergic neurons, known as starburst amacrine cells (SACs), play critical roles in the generation of precise neuronal activity in the retina and are located in the inner nuclear layer (INL, conventional) and ganglion cell layer (GCL, displaced). Methods: This study investigated the loss of and morphological changes in SACs in the retinas of streptozotocin (STZ)-induced diabetic and insulin-deficient C57BL/6-Tg(pH1-siRNAinsulin/CMV-hIDE)/Korl (IDCK) mice. SACs were immunocytochemically localized with anti-choline acetyltransferase (ChAT) antibody, and ChAT-labeled cells in the INL and GCL in the control and experimental groups were counted along the central vertical meridian in the whole-mounted retina using conventional fluorescent or confocal microscopes. Results: ChAT-immunoreactive (IR) neurons in STZ-induced diabetic mouse retina decreased by 8.34% at 4-6 weeks and by 14.89% at 42 weeks compared with the control group. Localized ChAT-IR neuron counts in the retinas of 20-week-old IDCK mice were 16.80% lower than those of age-matched control mice. Cell body deformation and aggregation were detected in the retinas of mice with DR. Single-cell injection experiments revealed the loss and deformation of dendritic branches in ChAT-IR neurons in DR. All ChAT-IR neurons expressed the calcium-binding protein calretinin, whereas no ChAT-IR neuron colocalized with calbindin-D28K or parvalbumin. Conclusions: Our results revealed that the neurodegenerative effects of the loss and deformation of ChAT-IR neurons can provide a reference for future study of this disease.
KW - calcium-binding proteins
KW - choline acetyltransferase
KW - diabetic retinopathy
KW - immunocytochemistry
KW - starburst amacrine cells
KW - streptozotocin
UR - http://www.scopus.com/inward/record.url?scp=85160694321&partnerID=8YFLogxK
U2 - 10.31083/j.fbl2805092
DO - 10.31083/j.fbl2805092
M3 - Article
C2 - 37258479
AN - SCOPUS:85160694321
SN - 2768-6701
VL - 58
JO - Frontiers in Bioscience - Landmark
JF - Frontiers in Bioscience - Landmark
IS - 5
M1 - 92
ER -