Mitochondrial Impairment in Antibiotic Induced Toxic Optic Neuropathies

Abstract

There is growing evidence for the role of mitochondrial dysfunction in the toxic optic neuropathies. Due to the structural similarities between antibiotic targets and mitochondrial machinery, several antibiotics known to cause optic neuropathy have deleterious effects on mitochondrial function. We review the literature on the prevalence, clinical manifestations, and management of antibiotic induced toxic optic neuropathies. The effect of these antibiotics on mitochondrial function in regard to the optic nerve is discussed.

Delayed and reversible ethambutol optic neuropathy

“…The painless development of decreased visual acuity with central and paracentral scotomas 4 , 5 in this patient in the absence of nutritional deficiency, lifestyle risk factors, or any other known ongoing pathology (apart from hypertension, which has been noted in previous case reports without identification as a formal risk factor for ethambutol optic neuropathy 6 ) and in the presence of ongoing ethambutol therapy fits the accepted characterization of ethambutol toxic optic neuropathy. 1 Other differential diagnoses included nutritional and hereditary optic neuropathies. Regarding nutritional causes, the patient's normal-range BMI and negative lab workup for anemia and vitamin B12 deficiency suggest against a nutritional deficiency as the cause, which could explain why supplemental therapy (the mainstay of treatment for nutritional optic neuropathies, seen in vitamin B12, folate, copper, and thiamine deficiencies 7 ) was not pursued.…”

“…A renowned complication of ethambutol treatment is the development of toxic optic neuropathy, which is believed to be secondary to the drug's metal chelating effects leading to mitochondrial toxicity. 1 , 2 The reported incidence of this complication at various doses ranges from <1% to >35%. 3 , 4 , 5 Due to the severe impact that this side effect has on patients' vision, monitoring for optic neuropathy through routine vision assessments and patient education is needed in all who use this medication, as is a baseline visual function assessment before starting treatment.…”

Ribosome‐targeting antibacterial agents: Advances, challenges, and opportunities

“…Most macrolides, such as roxithromycin, indiscriminately kill the beneficial bacteria in the intestine, which greatly reduce the microbial diversity of the small intestine and cecum and cause gastrointestinal symptoms 100 . Macrolide antibiotics also cause neurotoxicity (including central neurotoxicity and retinal toxicity) by binding to mitochondrial ribosome G2058 and other bases and inhibiting mitochondrial protein synthesis 91,101,102 …”

“…This impact can last for up to 2 years, causing long‐term damage to the patient 114 . Chloramphenicol can nonselectively inhibit mitochondrial ribosomes, leading to a series of side effects, such as retinal toxicity, vision loss, severe central blind spots, optic nerve edema, retinal hemorrhage, and retinal blood vessel tortuosity 102 …”

Длительная Нейропротекция Зрительного Нерва После Токсического Поражения Метанолом (Экспериментально-Клинические Наблюдения)

“…Ряд авторов в своих исследованиях, проведенных ранее, также высказывали предположение о повреждении митохондрий в сетчатке и ЗН, вызванном острым отравлением метанолом экспериментальных животных, приводящим к структурно-функциональным нарушениям в этих структурах [10][11][12]21]. При этом именно Yu J.J. (2018) считает, что повреждение аксонов НВ ведет к дистрофии сетчатки [22]. Или, наоборот, изменения, возникшие в сосудистой оболочке и наружных слоях сетчатки, как показали наши предыдущие работы [13], приводят к деструкции ганглиозных клеток и в дальнейшем к атрофии ЗН и патологии всего зрительного пути.…”