*Article* **Long-Term Effects of Repetitive Mild Traumatic Injury on the Visual System in Wild-Type and TDP-43 Transgenic Mice**

**Kristina Pilipovi´c 1, Jelena Rajiˇc Bumber 1, Petra Dolenec 1, Nika Gržeta 1, Tamara Jankovi´c 1, Jasna Križ <sup>2</sup> and Gordana Župan 1,\***


**Abstract:** Little is known about the impairments and pathological changes in the visual system in mild brain trauma, especially repetitive mild traumatic brain injury (mTBI). The goal of this study was to examine and compare the effects of repeated head impacts on the neurodegeneration, axonal integrity, and glial activity in the optic tract (OT), as well as on neuronal preservation, glial responses, and synaptic organization in the lateral geniculate nucleus (LGN) and superior colliculus (SC), in wild-type mice and transgenic animals with overexpression of human TDP-43 mutant protein (TDP-43G348C) at 6 months after repeated closed head traumas. Animals were also assessed in the Barnes maze (BM) task. Neurodegeneration, axonal injury, and gliosis were detected in the OT of the injured animals of both genotypes. In the traumatized mice, myelination of surviving axons was mostly preserved, and the expression of neurofilament light chain was unaffected. Repetitive mTBI did not induce changes in the LGN and the SC, nor did it affect the performance of the BM task in the traumatized wild-type and TDP-43 transgenic mice. Differences in neuropathological and behavioral assessments between the injured wild-type and TDP-43G348C mice were not revealed. Results of the current study suggest that repetitive mTBI was associated with chronic damage and inflammation in the OT in wild-type and TDP-43G348C mice, which were not accompanied with behavioral problems and were not affected by the TDP-43 genotype, while the LGN and the SC remained preserved in the used experimental conditions.

**Keywords:** brain injuries; traumatic; diffuse axonal injury; geniculate bodies; mice; nerve degeneration; neurofilament proteins; neuroglia; optic tract; superior colliculi; synaptophysin; TDP-43 proteinopathies
