title: Experimental study of local inner ear gene therapy for controlling autoimmune sensorineural hearing loss.
abstract: This study aimed to investigate the efficacy of gene therapy for treating autoimmune sensorineural hearing loss (ASHL) via local administration of a recombinant adenovirus vector containing the Fas ligand or interleukin IL-10 gene. Guinea pigs were divided into four groups, with different microinjections in the scala tympani. Group A were injected with FasL-EGFP, B with IL-10-EGFP, C with EGFP, and D with artificial perilymph. Seven days later, auditory brain-stem response (ABR) was tested, and the temporal bone was stained and observed by light microscopy. The spiral ligament and basement membrane were observed using transmission electron microscopy. FasL and IL-10 expression were examined using immunofluorescence histochemistry. Immunohistochemical analysis showed that the recombinant adenovirus vector in Groups A, B, and C can transfect the stria vascularis, the spiral ligament, the organ of Corti, the spiral ganglion, the region surrounding the small blood vessel in the modiolus, and the cochlear bone wall. Compared with those in Groups C and D, the ABR wave III mean thresholds were significantly lower and the inner ear immunoinflammatory responses in Groups A and B were significantly alleviated. Inhibition of immunoinflammatory response alleviated immunoinflammatory injury and auditory dysfunction. This technique shows potential as a novel therapy for ASHL.
authors.affiliation: State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, No. 5 Xinmofan Road, Nanjing, Jiangsu 210009, China.
authors.forename: Chang-qiang
authors.initials: CQ
authors.lastname: Tan
authors.affiliation: Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Jiangsu 210008, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Otolaryngology, Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu 210009, China.
authors.forename: Wen-jun
authors.initials: WJ
authors.lastname: Cai
authors.affiliation: Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Jiangsu 210008, China.
authors.forename: Xiao-yun
authors.initials: XY
authors.lastname: Qian
authors.affiliation: Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Jiangsu 210008, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, No. 5 Xinmofan Road, Nanjing, Jiangsu 210009, China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
mesh_terms: D000256:Adenoviridae; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D053222:Fas Ligand Protein / Q000096:biosynthesis* / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013136:Spiral Ganglion / Q000378:metabolism* / Q000473:pathology
chemical_list: D053222:Fas Ligand Protein; D011993:Recombinant Fusion Proteins; D016753:Interleukin-10