zithromax and Retinal-Diseases

Uveitis is one of the most common blindness-causing ocular disorders. Due to its complicated pathogenesis, the treatment of uveitis has been widely recognized as a challenge for ophthalmologists. Recently, the anti-inflammatory properties of the antibiotic Azithromycin (AZM) have been reported. However, the therapeutic effects of Azithromycin in experimental autoimmune uveitis (EAU), a representative model of human AU, have not been elucidated till date. We conducted this study to examine the therapeutic effects and potential mechanisms of Azithromycin in EAU. We observed that Azithromycin significantly attenuated retinal inflammation in EAU mice at day 14 after immunization along with a significantly decreased inflammatory cell infiltration and cytokine production in the retina. Furthermore, we observed that Azithromycin increased the number of regulatory T cells (Treg) and decreased the number of effector T cells (Teff) in both the draining lymph nodes and spleen of EAU mice. Additionally, Azithromycin suppressed the proliferation and activation of CD4 + T cells, and induced the apoptosis of CD4 + CD44 + memory T and CD4 + CXCR3 + Th1 cells. Mechanistically, we proved that Azithromycin could regulate Teff/Treg balance by inhibiting the phosphorylation of S6 ribosomal protein, a downstream target of mammalian target of rapamycin (mTOR). Together, our findings revealed that Azithromycin alleviated EAU by regulating the Teff/Treg balance through the mTOR signaling pathway, suggesting that Azithromycin could be a promising therapeutic candidate for AU.

Topics: Adoptive Transfer; Animals; Anti-Bacterial Agents; Apoptosis; Azithromycin; Cell Proliferation; Female; Gene Expression Regulation; Inflammation; Mice; Mice, Inbred C57BL; Peptide Fragments; Retinal Diseases; Retinol-Binding Proteins; T-Lymphocyte Subsets; TOR Serine-Threonine Kinases; Transcriptome

Retinal ischemic phenomena occur in several ocular diseases that share the degeneration and death of retinal ganglion cells (RGCs) as the final event. We tested the neuroprotective effect of azithromycin, a widely used semisynthetic macrolide antibiotic endowed with anti-inflammatory and immunomodulatory properties, in a model of retinal ischemic injury induced by transient elevation of intraocular pressure in the rat.. Retinal ischemia was induced in adult rats with transient elevation of intraocular pressure. RGCs were retrogradely labeled with Fluoro-Gold, and survival was assessed following a single dose of azithromycin given systemically at the end of the ischemia. The expression of death-associated proteins and extracellular signal-regulated kinase (ERK) activation was studied with western blotting. Expression and activity of matrix metalloproteinase-2 (MMP-2) and -9 were analyzed with gelatin zymography.. Acute post-injury administration of azithromycin significantly prevented RGC death. This effect was accompanied by reduced calpain activity and prevention of Bcl-2-associated death promoter (Bad) upregulation. The observed neuroprotection was associated with a significant inhibition of MMP-2/-9 gelatinolytic activity and ERK1/2 phosphorylation.. Azithromycin provides neuroprotection by modifying the inflammatory state of the retina following ischemia/reperfusion injury suggesting potential for repurposing as a drug capable of limiting or preventing retinal neuronal damage.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Azithromycin; bcl-Associated Death Protein; Blotting, Western; Calpain; Cell Survival; Cytoprotection; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neuroprotective Agents; Phosphorylation; Rats; Rats, Wistar; Reperfusion Injury; Retinal Diseases; Retinal Ganglion Cells

Vasoproliferative retinal tumors are benign tumors of unknown origin often accompanied by vitreoretinal inflammation. A 21-year-old female patient presented with acute reduced unilateral visual acuity. A solid yellow vascularized lesion was present in the inferior temporal retina accompanied by localized retinal detachment and accumulation of hard exudations. The only finding was an increased Bartonella henselae titer. Persistence of uveitis and blurred vision led to therapy for Bartonella henselae with macrolide antibiotics and successful tumor regression was achieved by cryotherapy.

Topics: Angiomatosis, Bacillary; Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Bartonella henselae; Combined Modality Therapy; Cryosurgery; Drug Therapy, Combination; Female; Fluorescein Angiography; Follow-Up Studies; Humans; Immunoglobulin G; Ophthalmoscopes; Retinal Detachment; Retinal Diseases; Retinal Neovascularization; Ultrasonography; Uveitis, Intermediate; Young Adult

Topics: Antibodies, Bacterial; Azithromycin; Bartonella henselae; Bell Palsy; Cat-Scratch Disease; Child; Drug Therapy, Combination; Eye Infections, Bacterial; Female; Fever of Unknown Origin; Glucocorticoids; Granuloma; Horner Syndrome; Humans; Immunoglobulin G; Prednisone; Retinal Diseases; Vision Disorders; Visual Acuity

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bartonella henselae; Cat-Scratch Disease; Female; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; Humans; Retinal Diseases; Scotoma; Time Factors; Visual Acuity