**16. Conclusion**

catalase (CAT), carried on recombinant adeno associated virus intravitreally in mice. The mice were euthanized and optic nerve volume, myelin fibre area, axonal cell loss and RGC loss evaluated Inital response showed a 15 fold increase in ECSOD and 3.3-fold in CAT [88]. After six months the authors reported 29% reduction in RGC loss, 36% in ON demyelination, and reduction in axonal loss by 44% all compared to control eyes, indicating that antioxidant gene

Administration of gene therapy must ideally be safe, repeatable, have low immunogenicity, and carry low infectious and mutagenic potential, modification of Koch's postulates [4]. Because viral vectors have the ability to maintain stable DNA within the target nucleus, they

*Adenoviral vectors (Ad*), non-enveloped replication-deficient recombinant viruses were the first to be used in gene therapy research [4,89]. They show high level of tropism for post mitotic and highly specialized cells, and have been known to reproduce TM cells with high accuracy. They have application in Muller cell and RPE cell replication as well. Studies have been done with Adenovirus (Ad) mediated intravitreal delivery of BDNF. However, repeated injections

*Adeno-associated Viruses (AAV).* This is an integrating vector known to show efficient delivery to target tissues. AAVs do not carry viral genes, therefore they have no unwanted pathoge‐ nicity, immunogenicity, nor significant inflammation upon sub retinal application [2]. In the last 4 years the use of AAV vector in the delivery of gene therapy has met some success in human trials, but the effect is limited to RGC survival. Though the vectors may target trabec‐

*Herpes Simplex Virus (HSV).* This virus has shown promise in glaucoma research and therapy as it is able to transduce trabecular meshwork,ciliary body epithelial, and retinal ganglion cells. The injected derivative however has been found to carry risks of inflammation, toxicity, and

*Lentiviral vectors.* These single strand RNA viruses can incorporate trabecular meshwork and RGC DNA by reverse transcription, with both neuroprotective and IOP lowering potential. Combining several enzymes such as cyclooxygenase and prostaglandin pathway enzymes

*Naked DNA Injection.* Work done with naked DNA as plasmid vectors expressing chloram‐ phenicol acetyl transferase has shown promise in the possible control of wound healing after trabeculectomy. The plasmid injected in the bleb or under collagen shield has resulted in a 30

have been found to cause severe inflammation in experimental models [2, 90]

ular meshwork cells, they are not very active there [89].

limited duration of gene expression [4].

increases their IOP-lowering properties. [90]

fold increase in the activity of the enzyme. [4].

*15.1.2. Non-viral vectors*

therapy will prove an invaluable adjunct to current glaucoma therapy.

**15.1. Administering gene therapy**

218 Glaucoma - Basic and Clinical Aspects

are preferred over non-viral vectors.

*15.1.1. Viral vectors*

The cause of glaucoma and ultimately retinal ganglion cell death is multifactorial. At present there is no cure for glaucoma and the mainstay of treatment medically and surgically is to control the IOP. However, this conventional approach of lowering IOP is merely a secondary or indirect approach to the real problem. Current studies show that glaucoma is a neurode‐ generative disease with neuroprotection and possibly neuroregeneration and neuro enhance‐ ment as the future treatment modality. Modified Koch's postulates have been applied in the experimental neuroprotective research. Ultimately the retinal ganglion cell death whether primary or secondary (bystander result) must be stopped and the neurons preserved. The clinical application of most of these experimental neuroprotective strategies still has yet to pass through randomized controlled clinical trials before they can be accepted. The future holds much promise as to possible effective neuroprotective strategies, however, much research is still yet to be done.
