Memantine mitigates ROS/TXNIP/NLRP3 signaling and protects against mouse diabetic retinopathy: Histopathologic, ultrastructural and bioinformatic studies.

Diabetic retinopathy (DRET) triggers vision loss in adults, however, little therapeutic options are existing. Memantine is an anti-Alzheimer drug that antagonizes the activity of glutamate at N-methyl-D-aspartate (NMDA) receptors. Glutamate and thioredoxin-interacting protein (TXNIP) are known to be overexpressed in diabetic retinas and can produce activation of NOD-like receptor protein 3 (NLRP3) with subsequent secretion of interlukin-1ß. This study repurposed memantine for its neuroprotective effect in experimental DRET and tested its impact on ROS/TXNIP/NLRP3. In addition, KEGG pathway database and STRING database identified the protein-protein interaction between glutamate receptors and TXNIP/NLRP3. Male Swiss albino mice received alloxan (180 mg/kg) to induce DRET. After 9 weeks, we divided the mice into groups: (a) saline, (ii) DRET, (iii and iv) DRET + oral memantine (5 or 10 mg per kg) for 28 days. Then, mice were euthanized, and eyeballs were removed. Retinal samples were utilized for biochemical, histopathological, and electron microscopy studies. Retinal levels of glutamate, TXNIP, NLRP3 and interlukin-1ß were estimated using ELISA technique as well as retinal malondialdehyde. Histopathological and ultrastructural examination demonstrated that oral memantine attenuated vacuolization and restored normal retinal cell layers. Moreover, memantine reduced TXNIP, NLRP3, interleukin-1ß and MDA concentrations. These results provide evidence demonstrating memantine' efficacy in alleviating DRET via suppressing reactive oxygen species/TXNIP/NLRP3 signaling cascade. Therefore, memantine might serve as a potential therapy for retinopathy after adequate clinical research.

Expression of CD3 and CD20 in Antistreptolysin-O Titer Seropositive and Seronegative Children with Chronic Tonsillitis.

Background: Chronic tonsillitis (CT) is a common inflammatory illness in children, and serum antistreptolysin O titer (ASOT) is a common investigation performed for these cases and considered a perfect sign for tonsillectomy. Objective: To evaluate the expression of tonsillar T-and B-lymphocytes markers in relation to seropositive or seronegative ASOT in cases of CT. Materials and Methods: Thirty children (15 males and 15 females) aged 6-10 years were divided equally into two groups: Group A seropositive ASOT (≥400 IU) and Group B seronegative ASOT (<400 IU). Both performed bilateral tonsillectomy. Specimens from the removed tonsils were taken and prepared for light microscopic examination and immunohistochemical evaluation of CD20 and CD3 expression. Results: Seropositive ASOT group showed significant histopathologic changes in the form of hyperplasia of the stratified squamous nonkeratinized epithelium, Urgas's abscess, and severe lymphocytic infiltration. Immunohistochemical results of seropositive ASOT group showed marked expression of CD3 and CD20, while seronegative ASOT group showed mild expression of CD3 and CD20. Conclusion: Seropositive ASOT CT, in addition to histopathological changes, is associated with significant increase in both B-lymphocytes (CD20 expression) and T-lymphocytes (CD3 expression) markers.