Hyaluronic Acid Enhances Gene Delivery into the Cochlea

Abstract Cochlear gene therapy can be a new avenue for the treatment of severe hearing loss by inducing regeneration or phenotypic rescue. One necessary step to establish this therapy is the development of a safe and feasible inoculation surgery, ideally without drilling the bony cochlear wall. The round window membrane (RWM) is accessible in the middle-ear space, but viral vectors placed on this membrane do not readily cross the membrane to the cochlear tissues. In an attempt to enhance permeability of the RWM, we applied hyaluronic acid (HA), a nontoxic and biodegradable reagent, onto the RWM of guinea pigs, prior to delivering an adenovirus carrying enhanced green fluorescent protein (eGFP) reporter gene (Ad-eGFP) at the same site. We examined distribution of eGFP in the cochlea 1 week after treatment, comparing delivery of the vector via the RWM, with or without HA, to delivery by a cochleostomy into the perilymph. We found that cochlear tissue treated with HA-assisted delivery of Ad-eGFP demonstrated wider expression of transgenes in cochlear cells than did tissue treated by cochleostomy injection. HA-assisted vector delivery facilitated expression in cells lining the scala media, which are less accessible and not transduced after perilymphatic injection. We assessed auditory function by measuring auditory brainstem responses and determined that thresholds were significantly better in the ears treated with HA-assisted Ad-eGFP placement on the RWM as compared with cochleostomy. Together, these data demonstrate that HA-assisted delivery of viral vectors provides an atraumatic and clinically feasible method to introduce transgenes into cochlear cells, thereby enhancing both research methods and future clinical application.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98453/1/hum%2E2011%2E086.pd

Hyaluronate Gel Stapedotomy

To evaluate hearing results and postoperative dizziness after stapedotomy with application of sodium hyaluronate gel (HG) to the oval window niche during fenestration of the footplate. Case-control study comparing 27 stapedotomies with HG and 32 stapedotomies without HG. Preoperative and postoperative audiometric data, postoperative dizziness (vertigo or dysequilibrium), and nystagmus. Postoperative hearing results were not statistically different for the 2 groups. There were no cases of postoperative sensorineural hearing loss greater than 10 dB. Early postoperative dizziness (chi(2) = 4.08, P = 0.043) and nystagmus (chi(2) = 5.05, P = 0.024) were reduced in the HG group. HG stapedotomy is safe and effective and results in less early postoperative dizziness and nystagmus when compared with the standard technique of stapedotomy. The application of HG to the oval window niche to prevent blood from entering or perilymph from escaping the vestibule during fenestration of the stapes footplate may contribute to a quicker recovery in outpatient otosclerosis surgery