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Glucose Homeostasis and Retinal Histopathology in CSAD KO Mice
Francoise Sidime1,2,3, Greg Phillips4,5, Nicole LaMassa4
1City University of New York Graduate School, College of Staten Island, Staten Island, NY, USA. francoise.sidime@csi.cuny.edu.
Abstract:
In this study we examined glucose homeostasis and retinal histology in homozygous knockout mice lacking CSAD (CSAD-KO). Two-month-old male mice were used including wild type (WT), homozygotes with without supplementation of taurine in the drinking water (1% w/v). Mice were sacrificed and the eyes processed for histology and immunohistochemistry. Additional mice were subjected to a glucose tolerance test (7.5 mg/kg BW) after 12 h fasting. We found that CSAD-KO and CSAD-KO treated with taurine were slightly hypoglycemic prior to glucose injection and showed a significantly reduced plasma glucose at 30, 60 and 120 min post-glucose injection, compared to WT. While glucose homeostasis in CSAD-KO was significantly different compared to WT, CSAD-KO supplemented with taurine was without effect. Analysis of retinas by electron microscopy showed that CSAD-KO without taurine supplementation exhibited substantial retinal degeneration. Remaining photoreceptor outer and inner segments were disorganized. Retinal nuclear and synaptic layers were largely absent and there was apparent reorganization of the pigmented epithelial cells. The choroid and sclera were intact. These histological aberrations were largely rectified by taurine supplementation in the drinking water.These data indicate that taurine deficiency alters glucose homeostasis and retinal structure and taurine supplementation improves these retinal abnormalities, but not in hypoglycemia.
Insights
Taurine deficiency in CSAD-KO mice disrupts glucose balance and causes severe retinal degeneration. Taurine supplementation corrects retinal issues but does not resolve hypoglycemia in these models.
Area of Science:
- Biochemistry
- Ophthalmology
- Metabolism
Background:
- Cystathionine beta-synthase (CBS) is crucial for taurine synthesis.
- Taurine plays vital roles in retinal function and glucose metabolism.
- CSAD-KO mice models offer insights into taurine deficiency-related pathologies.
Purpose of the Study:
- To investigate the impact of CSAD deficiency on glucose homeostasis.
- To analyze retinal histology in CSAD-KO mice.
- To determine the efficacy of taurine supplementation in mitigating CSAD deficiency effects.
Main Methods:
- Glucose tolerance tests were performed on CSAD-KO and wild-type mice.
- Retinal tissues were examined using electron microscopy and immunohistochemistry.
- Mice received either standard water or 1% taurine supplemented water.
Main Results:
- CSAD-KO mice exhibited hypoglycemia and impaired glucose tolerance compared to wild-type.
- Significant retinal degeneration, including photoreceptor disorganization, was observed in CSAD-KO mice without taurine.
- Taurine supplementation largely restored retinal structure but did not normalize glucose homeostasis.
Conclusions:
- Taurine deficiency significantly impacts both glucose metabolism and retinal integrity.
- Taurine supplementation is effective in ameliorating retinal abnormalities caused by CSAD deficiency.
- The study highlights the critical role of taurine in maintaining ocular health and metabolic balance.
