Intravitreal injection worsens outcomes in a mouse model of indirect traumatic optic neuropathy from closed globe injury

Purpose. Investigating the efficacy of intravitreal injection of erythropoietin (EPO) in managing indirect traumatic optic neuropathy (ITON) of different durations.Methods. A case series that included two groups of ITON patients: recent ITON group (<3 months trauma duration; 7 eyes) and old duration ITON group (3–36 months; 7 eyes). Diagnostic computerized tomography (CT) and baseline flash visual evoked response (VER) were performed at the presentation time. At the initial visit and each follow-up, all patients had undergone assessment of best-corrected visual acuity (BCVA), pupil reaction, and anterior and posterior segments. VER was repeated 1 and 3 months after injection. All patients received an intravitreal injection of 2000 IU EPO in 0.2 ml of commercially available sterile EPREX 4000 solution, Jansen Cilag, Zug, Switzerland. Five patients had received a second injection 3 months later.Results. Significant improvement was found in BCVA, VER amplitude, and latency (P<0.0001, 0.0154, and 0.0291, respectively). Initial values of BCVA, VER amplitude, and latency correlated significantly to the final values. Differences between recent and old trauma groups were insignificant in the three parameters. In patients who received second injection, further clinical but statistically insignificant improvement was noted in BCVA in 60% of patients, VER amplitude in 50% of patients, and in VER latency in 100% of patients. No complications were recorded.Conclusion. Intravitreal injection of EPO may be effective and safe in treatment of recent and old indirect traumatic optic neuropathy.

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Intravitreal Injection of Long-Acting Pegylated Granulocyte Colony-Stimulating Factor Provides Neuroprotective Effects via Antioxidant Response in a Rat Model of Traumatic Optic Neuropathy

Antioxidants ◽

10.3390/antiox10121934 ◽

2021 ◽

Vol 10 (12) ◽

pp. 1934

Author(s):

Chin-Te Huang ◽

Yao-Tseng Wen ◽

Tushar Dnyaneshwar Desai ◽

Rong-Kung Tsai

Keyword(s):

Optic Nerve ◽

Intravitreal Injection ◽

Optic Neuropathy ◽

Rat Model ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Traumatic Optic Neuropathy ◽

Neuroprotective Effects ◽

Long Acting ◽

Stimulating Factor

Traumatic optic neuropathy (TON) may cause severe visual loss following direct or indirect head trauma which may result in optic nerve injuries and therefore contribute to the subsequent loss of retinal ganglion cells by inflammatory mediators and reactive oxygen species (ROS). Granulocyte colony-stimulating factor (G-CSF) provides the anti-inflammatory and anti-oxidative actions but has a short half-life and also induces leukocytosis upon typical systemic administration. The purpose of the present study was to investigate the relationship between the anti-oxidative response and neuroprotective effects of long-acting pegylated human G-CSF (PEG-G-CSF) in a rat model of optic nerve crush (ONC). Adult male Wistar rats (150–180 g) were chosen to have a sham operation in one eye and have ONC in the other. PEG-G-CSF or phosphate-buffered saline (PBS control) was immediately administered after ONC by intravitreal injection (IVI). We found the IVI of PEG-G-CSF does not induce systemic leukocytosis, but increases survival of RGCs and preserves the visual function after ONC. TUNEL assays showed fewer apoptotic cells in the retina in the PEG-G-CSF-treated eyes. The number of sorely ED1-positive cells was attenuated at the lesion site in the PEG-G-CSF-treated eyes. Immunoblotting showed up-regulation of p-Akt1, Nrf2, Sirt3, and HO-1 in the ON of the PEG-G-CSF-treated eyes. Our results demonstrated that one IVI of long-acting PEG-G-CSF is neuroprotective in the rONC. PEG-G-CSF activates the p-Akt1/Nrf2/Sirt3 and the p-Akt1/Nrf2/HO-1 axes to provide the antioxidative action and further attenuated RGC apoptosis and neuroinflammation. This provides crucial preclinical information for the development of alternative therapy with IVI of PEG-G-CSF in TON.

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