title: Neuroprotective Effect of Magnesium Acetyltaurate Against NMDA-Induced Excitotoxicity in Rat Retina.
abstract: Glutamate excitotoxicity plays a major role in the loss of retinal ganglion cells (RGCs) in glaucoma. The toxic effects of glutamate on RGCs are mediated by the overstimulation of N-methyl-D-aspartate (NMDA) receptors. Accordingly, NMDA receptor antagonists have been suggested to inhibit excitotoxicity in RGCs and delay the progression and visual loss in glaucoma patients. The purpose of the present study was to examine the potential neuroprotective effect of Mg acetyltaurate (MgAT) on RGC death induced by NMDA. MgAT was proposed mainly due to the combination of magnesium (Mg) and taurine which may provide neuroprotection by dual mechanisms of action, i.e., inhibition of NMDA receptors and antioxidant effects. Rats were divided into 5 groups and were given intravitreal injections. Group 1 (PBS group) was injected with vehicle; group 2 (NMDA group) was injected with NMDA while groups 3 (pre-), 4 (co-), and 5 (post-) treatments were injected with MgAT, 24 h before, in combination or 24 h after NMDA injection respectively. NMDA and MgAT were injected in PBS at doses 160 and 320 nmol, respectively. Seven days after intravitreal injection, the histological changes in the retina were evaluated using hematoxylin & eosin (H&E) staining. Optic nerves were dissected and stained in Toluidine blue for grading on morphological neurodegenerative changes. The extent of apoptosis in retinal tissue was assessed by TUNEL assay and caspase-3 immunohistochemistry staining. The estimation of neurotrophic factor, oxidative stress, pro/anti-apoptotic factors and caspase-3 activity in retina was done using enzyme-linked immunosorbent assay (ELISA) technique. The retinal morphometry showed reduced thickness of ganglion cell layer (GCL) and reduction in the number of retinal cells in GCL in NMDA group compared to the MgAT-treated groups. TUNEL and caspase-3 staining showed increased number of apoptotic cells in inner retina. The results were further corroborated by the estimation of neurotrophic factor, oxidative stress, pro/anti-apoptotic factors, and caspase-3 activity in retina. In conclusion, current study revealed that intravitreal MgAT prevents retinal and optic nerve damage induced by NMDA. Overall, our data demonstrated that the pretreatment with MgAT was more effective than co- and posttreatment. This protective effect of MgAT against NMDA-induced retinal cell apoptosis could be attributed to the reduction of retinal oxidative stress and activation of BDNF-related neuroprotective mechanisms.
authors: Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital, Sungai Buloh Campus, Sungai Buloh, 47000, Selangor Darul Ehsan, Malaysia.
authors: Lidawani
authors: L
authors: Lambuk
authors: Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital, Sungai Buloh Campus, Sungai Buloh, 47000, Selangor Darul Ehsan, Malaysia.
authors: Azliana Jusnida Ahmad
authors: AJ
authors: Jafri
authors: Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital, Sungai Buloh Campus, Sungai Buloh, 47000, Selangor Darul Ehsan, Malaysia.
authors: Natasha Najwa Nor
authors: NN
authors: Arfuzir
authors: Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital, Sungai Buloh Campus, Sungai Buloh, 47000, Selangor Darul Ehsan, Malaysia. iezhitsa@yandex.ru.|Research Institute of Pharmacology, Volgograd State Medical University, 1, Pavshikh Bortsov sq., Volgograd, Russian Federation, 400131. iezhitsa@yandex.ru.
authors: Igor
authors: I
authors: Iezhitsa
authors: Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital, Sungai Buloh Campus, Sungai Buloh, 47000, Selangor Darul Ehsan, Malaysia.
authors: Renu
authors: R
authors: Agarwal
authors: Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital, Sungai Buloh Campus, Sungai Buloh, 47000, Selangor Darul Ehsan, Malaysia.
authors: Khairul Nizam Bin
authors: KN
authors: Rozali
authors: Department of Ophthalmology, IMU Clinical School, International Medical University, Jalan Rasah, Seremban, Malaysia.
authors: Puneet
authors: P
authors: Agarwal
authors: Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital, Sungai Buloh Campus, Sungai Buloh, 47000, Selangor Darul Ehsan, Malaysia.
authors: Nor Salmah
authors: NS
authors: Bakar
authors: Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital, Sungai Buloh Campus, Sungai Buloh, 47000, Selangor Darul Ehsan, Malaysia.
authors: Methil Kannan
authors: MK
authors: Kutty
authors: Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital, Sungai Buloh Campus, Sungai Buloh, 47000, Selangor Darul Ehsan, Malaysia.
authors: Ahmad Pauzi Md
authors: AP
authors: Yusof
authors: Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital, Sungai Buloh Campus, Sungai Buloh, 47000, Selangor Darul Ehsan, Malaysia.
authors: Anna
authors: A
authors: Krasilnikova
authors: Research Institute of Pharmacology, Volgograd State Medical University, 1, Pavshikh Bortsov sq., Volgograd, Russian Federation, 400131.
authors: Alexander
authors: A
authors: Spasov
authors: Research Institute of Pharmacology, Volgograd State Medical University, 1, Pavshikh Bortsov sq., Volgograd, Russian Federation, 400131.
authors: Alexander
authors: A
authors: Ozerov
authors: Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital, Sungai Buloh Campus, Sungai Buloh, 47000, Selangor Darul Ehsan, Malaysia.
authors: Nafeeza Mohd
authors: NM
authors: Ismail
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D058449:Intravitreal Injections; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; C083076:acetyltaurine; D013654:Taurine; D016202:N-Methylaspartate
keywords: Excitotoxicity; Glaucoma; Magnesium acetyltaurate; NMDA; Neuroprotection; RGC apoptosis