Mohd Aizuddin Mohd Lazaldin1, Igor Iezhitsa1,2, Renu Agarwal1, Nor Salmah Bakar1, Puneet Agarwal3, Nafeeza Mohd Ismail1. 1. a Centre For Neuroscience Research, Faculty of Medicine , Universiti Teknologi MARA, Sungai Buloh Campus, Selangor , Malaysia. 2. b Research Institute of Pharmacology, Volgograd State Medical University , Volgograd , Russia. 3. c IMU Clinical School, International Medical University , Seremban , Malaysia.
Abstract
PURPOSE: Amyloid beta (Aβ) is known to contribute to the pathophysiology of retinal neurodegenerative diseases such as glaucoma. Effects of intravitreal Aβ(1-42) on retinal and optic nerve morphology in animal models have widely been studied but not those of Aβ(1-40). Hence, we evaluated the time- and dose-related effects of intravitreal Aβ(1-40) on retinal and optic nerve morphology. Since oxidative stress and brain derived neurotrophic factor (BDNF) are associated with Aβ-induced neuronal damage, we also studied dose and time-related effects of Aβ(1-40) on retinal oxidative stress and BDNF levels. MATERIALS AND METHODS: Five groups of rats were intravitreally administered with vehicle or Aβ(1-40) in doses of 1.0, 2.5, 5 and 10 nmol. Animals were sacrificed and eyes were enucleated at weeks 1, 2 and 4 post-injection. The retinae were subjected to morphometric analysis and TUNEL staining. Optic nerve sections were stained with toluidine blue and were graded for neurodegenerative effects. The estimation of BDNF and markers of oxidative stress in retina were done using ELISA technique. RESULTS AND CONCLUSIONS: It was observed that intravitreal Aβ(1-40) causes significant retinal and optic nerve damage up to day 14 post-injection and there was increasing damage with increase in dose. However, on day 30 post-injection both the retinal and optic nerve morphology showed a trend towards normalization. The observations made for retinal cell apoptosis, retinal glutathione, superoxide dismutase activity and BDNF were in accordance with those of morphological changes with deterioration till day 14 and recovery by day 30 post-injection. The findings of this study may provide a guide for selection of appropriate experimental conditions for future studies.
PURPOSE: Amyloid beta (Aβ) is known to contribute to the pathophysiology of retinal neurodegenerative diseases such as glaucoma. Effects of intravitreal Aβ(1-42) on retinal and optic nerve morphology in animal models have widely been studied but not those of Aβ(1-40). Hence, we evaluated the time- and dose-related effects of intravitreal Aβ(1-40) on retinal and optic nerve morphology. Since oxidative stress and brain derived neurotrophic factor (BDNF) are associated with Aβ-induced neuronal damage, we also studied dose and time-related effects of Aβ(1-40) on retinal oxidative stress and BDNF levels. MATERIALS AND METHODS: Five groups of rats were intravitreally administered with vehicle or Aβ(1-40) in doses of 1.0, 2.5, 5 and 10 nmol. Animals were sacrificed and eyes were enucleated at weeks 1, 2 and 4 post-injection. The retinae were subjected to morphometric analysis and TUNEL staining. Optic nerve sections were stained with toluidine blue and were graded for neurodegenerative effects. The estimation of BDNF and markers of oxidative stress in retina were done using ELISA technique. RESULTS AND CONCLUSIONS: It was observed that intravitreal Aβ(1-40) causes significant retinal and optic nerve damage up to day 14 post-injection and there was increasing damage with increase in dose. However, on day 30 post-injection both the retinal and optic nerve morphology showed a trend towards normalization. The observations made for retinal cell apoptosis, retinal glutathione, superoxide dismutase activity and BDNF were in accordance with those of morphological changes with deterioration till day 14 and recovery by day 30 post-injection. The findings of this study may provide a guide for selection of appropriate experimental conditions for future studies.
Authors: Mohamad Haiqal Nizar Mohamad; Izuddin Fahmy Abu; Muhammad Fattah Fazel; Renu Agarwal; Igor Iezhitsa; Norsham Juliana; Ian R Mellor; Henrik Franzyk Journal: Front Pharmacol Date: 2021-12-14 Impact factor: 5.810
Authors: Mohd Aizuddin Mohd Lazaldin; Igor Iezhitsa; Renu Agarwal; Puneet Agarwal; Nafeeza Mohd Ismail Journal: Neural Regen Res Date: 2023-02 Impact factor: 6.058
Authors: Xiaowei Wang; Nanhong Lou; Allison Eberhardt; Yujia Yang; Peter Kusk; Qiwu Xu; Benjamin Förstera; Sisi Peng; Meng Shi; Antonio Ladrón-de-Guevara; Christine Delle; Björn Sigurdsson; Anna L R Xavier; Ali Ertürk; Richard T Libby; Lu Chen; Alexander S Thrane; Maiken Nedergaard Journal: Sci Transl Med Date: 2020-03-25 Impact factor: 17.956