Chapter 19, Problem 24COQ

Summary Introduction

To determine:

The characteristics of blindness that make LCA an attractive candidate for gene therapy treatment.

Concept Introduction:

The insertion of the genetic material (DNA) into the cells of patient (human) for the treatment of particular disorder is known as gene therapy. The procedure of the gene therapy includes a patient who is given healthy genes to make up for the diseased gene or faulty gene.

Explanation of Solution

Researchers have suggested that half of blindness cases in adults before age 45 are due to heredity. Because of nerves associated with eyes, brain parts involved in visual perception and complexity of eye, defects could occur in various genes that may result in blindness. Leber congenital amaurosis (LCA) is a form of blindness which is inherited to offspring by parents as autosomal recessive disorder.

LCA occurs when there is a defect or mutation in one of the genes responsible for functioning and development of photo receptors cells in retina. Children with two defective copies of gene begin to lose eyesight at birth as light sensing cells die and become blind before the age of 40. There is another type of LCA which is caused by defective RPE65 gene. This gene is responsible for converting vitamin A into a light absorbing pigment called rhodopsin.

LCA disorder can be treated by the help of gene therapy. The characteristics of retinal blindness such as LCA that makes it suitable for gene therapy are:

(1) Retina consists of an ordered layer of epithelial cells which make it easier for administrating therapeutic gene containing DNA vector in eye cell population.

(2) The retinal tissue is smaller than visceral organ. This feature of retinal tissue permits a targeted and efficient approach for insertion of DNA vector inside cells.

(3) The intraocular environment is separated or isolated from immune system by the blood-retinal barrier. It is important to prevent any extreme immune response on insertion of foreign antigen.

(4) The very slow rate of retinal cells division makes it possible for using non-integrating vectors which facilitate sustained expression of transgene used in gene therapy.

Conclusion

The characteristics of retinal cells such as compact epithelial layer, small retinal tissue, separation of intraocular environment from immune system and slow rate of retinal cell division, makes treatment of retinal blindness such as LCA suitable for gene therapy.