Book review

Retinal dystrophies: functional genomics togene therapyGregory Bock, Gerry Chader and Jamie Goode (eds)

John Wiley & Sons, 2004. $ 160, 216 pp. ISBN 0-470-85357-3

This book reports the proceedings of the Novartis Foundation

Symposium 25, held in Baltimore, MD on 21–23 October

2002. It consists of an Introduction, 13 chapters (207

pages) and indices. Each chapter is followed by a transcript

of the discussion with each discussant identified and refer-

ences cited.

Retinal dystrophies (RD), the major causes of incurable

blindness in Europe and North America, are disorders of

photoreceptors and/or the retinal pigment epithelium, which

include age-related macular degeneration, cone dystrophy,

congenital stationary night blindness, macular dystrophy

and retinitis pigmentosa. Many popular inbred mouse strains

carry mutations causing RD (e.g. FVB and C3H). This book

focuses on four areas of research related to the genes and

loci associated with RD: genetic mutations underlying RD;

functional genomics – the study of the biochemical and

cellular pathways regulated by these gene mutations; animal

models of retinal disorders and gene therapy approaches to

treating RD through transplantation, pharmacogenomics and

modulating faulty genes.

The genetic approach to RD has been facilitated by the

Human Genome Project and by the development of

Bioinformatics but is hampered by the problem of genetic

heterogeneity, a theme expanded by Daiger who discusses

the complexity of the genetic basis of retinal diseases due

to genetic, allelic, phenotypic and clinical heterogeneity.

Reference to RetNet, the Retinal Information Network,

maintained by Daiger, shows that as of January 2005,

158 genes affecting RD have been identified and 110

cloned. RetNet is a valuable link to diseases of the retina

and their genetic bases and provides tables of genes

causing inherited retinal diseases, such as retinitis

pigmentosa, macular degeneration and Usher syndrome,

and related information for research purposes. The use of

gene microarrays to detect genes involved in retinal

development and degeneration and bioinformatic analyses

of large expressed sequence tag databases for gene

discovery, and expression profiling are discussed by

Chowers et al. with a focus on the use of gene expression

profiling in the developing and adult retina.

There are three chapters on functional genomics. Hunt et al.

examine the genetic regulation of cGMP levels in phototrans-

duction. Molday et al. examine the role of Peripherin 2, a

photoreceptor-specific membrane protein linked to autosomal

dominant retinitis pigmentosa, using transgenic Xenopus lae-

vis tadpole rod photoreceptors, a relatively new animal model.

Yu et al. provide a progress report on their search for the

biochemical changes resulting from deleterious gene muta-

tions in retina and retinal pigment epithelium in humans and

mice. It is unfortunate that the concept of RD is not defined

until this chapter (page 147). Rather than gene-based thera-

pies for treating RD, these authors advocate therapies based

on the changes in cellular pathways leading to photoreceptor

cell death by apoptosis. Functional genomic analysis of the

gene products is expected to lead to new treatments for

retinal and macular degeneration.

There is no single chapter in the book on animal models for

research on retinal degeneration. Many animal models are,

however, discussed: from Drosophila to transgenic Xenopus

laevis tadpoles, chicks, the RCS rdy rat, numerous transgenic

mouse models (e.g. rds –/–, RPE65 –/–, abcr –/–, irbp –/–,

Brn3b –/– and Crx –/– mice) and the Briard RPE65 dog

model. It would have been useful to have a chapter on the

advantages and disadvantages of different animal models,

but the paper of Chader (2002) must suffice.

The majority of the chapters (seven) are on various

approaches to gene therapy for RD. Radu et al. provide evi-

dence that isoretinoin (Accutane) inhibits the accumulation of

lipofuscin and delays the onset of visual loss in the abcr –/–

mouse model. Bok discusses gene replacement therapy in

rds –/– mice, the Briard dog and the RCS (rdy) rat and gene-

based trophic factor therapy using CNTF. Leveillard et al.

examine how the degeneration of rods can lead to cone

degeneration through rod–cone interactions in the rd1

mouse, which has lost the function of PDE6B. Three types

of therapeutic approaches for improving vision in this mouse

are discussed: retinal transplants, gene therapy and pharma-

cotherapy. Ali promotes the use of adenovirus associated viral

vectors for gene transfer but notes that there are currently no

effective gene treatments for these diseases in humans.

Hauswith et al. suggest that different strategies need to be

developed for dominant gene deficits, recessive gene deficits

and retinal diseaseswith complex or unknown genetic origins.

Bennett discusses ‘Gene therapy for Leber congenital

amaurosis’ in the RPE65 mutant dog. The success of improv-

ing vision in this dog by using a adeno-associated virus indi-

cates that gene therapy is able to deliver a corrective gene to a

target retinal cell and that this gene can functionally activate

biochemical and cellular functions which lead to improved

vision.

This book is difficult to evaluate, as it consists of the

proceedings of a meeting and the chapters are not organized

Genes, Brain and Behavior (2005) 4: 399–400 Copyright # Blackwell Munksgaard 2005

doi: 10.1111/j.1601-183X.2005.00158.x 399

into sections. It may be hard to understand if you are a

novice in the abbreviations used in retinal research. Apart

from the difficulty in keeping up with the abbreviations, my

biggest complaint was that the book was not organized sys-

tematically, despite the outline in the introduction. I used the

RetNet website to get background information for some of

the chapters and looked up references on PubMed to help

with others. Clearly, this is not a book for the general reader but

for the researcher in retinal disorders who is familiar with the

genetic issues involved. The advantages of such a volume are

that there is a concentration of papers on a single topic in a single

volume, and there is adiscussionof the topics after eachchapter.

The disadvantages are that the chapters do not contain the

procedural detailsof a journal articleand thatmanyof thediscussion

points have been superseded by work published since the confer-

ence was held. For its size, the book is on the expensive side.

Richard E. Brown

Department of Psychology

Dalhousie University

Halifax, Nova Scotia

Canada B3H 4J1

E-mail: rebrown@dal.ca

Reference

Chader, G.J. (2002) Animal models in research on retinal

degenerations: past progress and future hope. Vision Res

42, 393–399.

Book review

400 Genes, Brain and Behavior (2005) 4: 399–400