title: Early postnatal virus inoculation into the scala media achieved extensive expression of exogenous green fluorescent protein in the inner ear and preserved auditory brainstem response thresholds.
abstract: BACKGROUND
  Gene transfer into the inner ear is a promising approach for treating sensorineural hearing loss. The special electrochemical environment of the scala media raises a formidable challenge for effective gene delivery at the same time as keeping normal cochlear function intact. The present study aimed to define a suitable strategy for preserving hearing after viral inoculation directly into the scala media performed at various postnatal developmental stages.
  
  
  METHODS
  We assessed transgene expression of green fluorescent protein (GFP) mediated by various types of adeno-associated virus (AAV) and lentivirus (LV) in the mouse cochlea. Auditory brainstem responses were measured 30 days after inoculation to assess effects on hearing.
  
  
  RESULTS
  Patterns of GFP expression confirmed extensive exogenous gene expression in various types of cells lining the endolymphatic space. The use of different viral vectors and promoters resulted in specific cellular GFP expression patterns. AAV2/1 with cytomegalovirus promoter apparently gave the best results for GFP expression in the supporting cells. Histological examination showed normal cochlear morphology and no hair cell loss after either AAV or LV injections. We found that hearing thresholds were not significantly changed when the injections were performed in mice younger than postnatal day 5, regardless of the type of virus tested.
  
  
  CONCLUSIONS
  Viral inoculation and expression in the inner ear for the restoration of hearing must not damage cochlear function. Using normal hearing mice as a model, we have achieved this necessary step, which is required for the treatment of many types of congenital deafness that require early intervention.
authors: Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, PR China.
authors: Yunfeng
authors: Y
authors: Wang
authors: Yu
authors: Y
authors: Sun
authors: Qing
authors: Q
authors: Chang
authors: Shoeb
authors: S
authors: Ahmad
authors: Binfei
authors: B
authors: Zhou
authors: Yeunjung
authors: Y
authors: Kim
authors: Huawei
authors: H
authors: Li
authors: Xi
authors: X
authors: Lin
mesh_terms: D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects* / Q000502:physiology; D003053:Cochlear Duct / Q000378:metabolism*; D000229:Dependovirus; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006319:Hearing Loss, Sensorineural / Q000628:therapy*; D006652:Histological Techniques; D016086:Lentivirus; D051379:Mice; D019076:Transgenes / Q000235:genetics
chemical_list: D049452:Green Fluorescent Proteins