0
November 1993, Vol 111, No. 11 >
ARTICLE | November 1993

Ocular Gene Therapy: Title and subTitle BreakFrom Fantasy to Foreseeable Reality FREE

Donald J. Zack, MD, PhD
Arch Ophthalmol. 1993;111(11):1477-1479. doi:10.1001/archopht.1993.01090110043019
Text Size: A A A
Published online
Article
References
Comments

THIS ISSUE of the Archives commemorates the 40th anniversary of the publication of Watson and Crick's1 classic paper on the structure of DNA. In 1953, gene therapy was mentioned only in the realm of science fiction. Now, a mere 40 years later, gene therapy has become a reality.2 A number of clinical trials are already in progress, and the number of proposed trials is increasing almost daily.2-5 Current trials involve diseases as diverse as severe combined immunodeficiency, cancer, and cystic fibrosis. Although to date none of these trials involves the eye, this situation is sure to change in the near future. (In one sense, ocular gene therapy is already a reality. The murine retinal degeneration [rd] and retinal degeneration slow [rds] mutations have been "rescued" using transgenic mouse technology.6,7 However, transgenesis involves germ line transformation and is not directly applicable to human gene therapy.)

Genetic disease

REFERENCES

1 +
Watson JD, Crick FHC.  Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid . Nature . 1953;;171:737-738.
2 +
Culotta E.  New startups move in as gene therapy goes commercial . Science . 1993;;260:914-915.
3 +
Anderson WF.  Human gene therapy . Science . 1992;;256:808-813.
4 +
Miller AD.  Human gene therapy comes of age . Nature . 1992;;357:455-460.
5 +
Mulligan RC.  The basic science of gene therapy . Science . 1993;;260:926-932.
6 +
Lem J, Flannery JG, Li T, Applebury ML, Farber DB, Simon MI.  Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase beta subunit . Proc Natl Acad Sci U S A . 1992;;15:4422-4426.
7 +
Travis GH, Groshan KR, Lloyd M, Bok D.  Complete rescue of photoreceptor dysplasia and degeneration in transgenic retinal degeneration slow (rds) mice . Neuron . 1992;;9:113-119.
8 +
Kaiser-Kupfer MI, Caruso RC, Valle D.  Gyrate atrophy of the choroid and retina: long-term reduction of ornithine slows retinal degeneration . Arch Ophthalmol . 1991;;109:1539-1548.
9 +
Bok D.  Retinal transplantation and gene therapy: present realities and future possibilities . Invest Ophthalmol Vis Sci . 1993;;34:473-476.
10 +
Rosenfeld P, Cowley G, McGee T, Sandberg M, Berson E, Dryja T.  A null mutation in the rhodopsin gene causes rod photoreceptor dysfunction and autosomal recessive retinitis pigmentosa . Nature Genet . 1992;;1:209-213.
11 +
Musarella MA.  Gene mapping of ocular diseases . Surv Ophthalmol . 1992;;36:285-312.
12 +
Dryja TP, McGee TL, Hahn LB, et al.  Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa . N Engl J Med . 1990;;323:1302-1307.
13 +
Dryja TP, McGee TL, Reichel E, et al.  A point mutation of the rhodopsin gene in one form of retinitis pigmentosa . Nature . 1990;;343:364-366.
14 +
Sung C-H, Davenport CM, Hennesey JC, et al.  Rhodopsin mutations in autosomal dominant retinitis pigmentosa . Proc Natl Acad Sci U S A . 1991;;88:6481-6485.
15 +
Sheffield V, Fishman G, Beck J, Kimura A.  Identification of novel rhodopsin mutations associated with retinitis pigmentosa using GC-clamped denaturing gradient gel electrophoresis . Am J Hum Genet . 1991;;49:699-706.
16 +
McLaughlin ME, Sandberg MA, Berson EL, Dryja TP.  Recessive mutations in the gene encoding the β-subunit of rod phosphodiesterase in patients with retinitis pigmentosa . Nature Genet . 1993;;4:130-134.
17 +
Kajiwara K, Sandberg MA, Berson EL, Dryja TP.  A null mutation in the human peripherin/RDS gene in a family with autosomal dominant retinitis punctata albescens . Nature Genet . 1993;;3:208-212.
18 +
Nichols BE, Sheffield VC, Vandenburgh K, Drack AV, Kimura AE, Stone EM.  Butterfly-shaped pigment dystrophy of the fovea caused by a point mutation in codon 167 of the RDS gene . Nature Genet . 1993;;3:202-207.
19 +
Wells J, Wroblewski J, Keen J, et al.  Mutations in the human retinal degeneration slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy . Nature Genet . 1993;;3:213-218.
20 +
Berger W, Meindl A, van de Pol TJR, et al.  Isolation of a candidate gene for Norrie disease by positional cloning . Nature Genet . 1992;;1:199-203.
21 +
Chen Z-Y, Hendriks RW, Jobling MA, et al.  Isolation and characterization of a candidate gene for Norrie disease . Nature Genet . 1992;;1:204-208.
22 +
Nathans J, Davenport CM, Maumenee IH, et al.  Molecular genetics of human blue cone monochromacy . Science . 1989;;245:831-838.
23 +
Cremers FPM, van de Pol DJ, van Kerkhoff LP, Wieringa B, Ropers HH.  Cloning of a gene that is rearranged in patients with choroideremia . Nature . 1990;;347:674-677.
24 +
Merry DE, Janne PA, Landers JE, Lewis RA, Nussbaum RL.  Isolation of a candidate gene for choroideremia . Proc Natl Acad Sci U S A . 1992;;89:2135-2139.
25 +
Akli A, Caillaud C, Vigne E, et al.  Transfer of a foreign gene into the brain using adenovirus vectors . Nature Genet . 1993;;3:224-228.
26 +
Bajocchi G, Feldman SH, Crystal RG, Mastrangeli A.  Direct in vivo gene transfer to ependymal cells in the central nervous system using recombinant adenovirus vectors . Nature Genet . 1993;;3:229-234.
27 +
Davidson BL, Allen ED, Kozarsky KF, Wilson JM, Roessler BJ.  A model system for in vivo gene transfer into the central nervous system using an adenoviral vector . Nature Genet . 1993;;3:219-223.
28 +
Wagner E, Zatloukal K, Cotten M, et al.  Coupling of adenovirus to transferrin-polylysine/DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected genes . Proc Natl Acad Sci U S A . 1992;;89:6099-6103.
29 +
Zack DJ, Bennett J, Wang Y, et al.  Unusual topography of bovine rhodopsin promoter-lacZ fusion gene expression in transgenic mouse retinas . Neuron . 1991;;6:187-199.
30 +
Zack DJ. Analysis of retinal-specific gene expression in transgenic mice. In: Hargrave PA, ed. Methods in Neuroscience: Photoreceptor Cells. Orlando, Fla: Academic Press Inc. In press.
31 +
Lem J, Applebury ML, Falk JD, Flannery JG, Simon MI.  Tissue-specific and developmental regulation of rod opsin chimeric genes in transgenic mice . Neuron . 1991;;6:201-210.
32 +
Olsson JE, Gordon JW, Pawlyk BS, et al.  Transgenic mice with a rhodopsin mutation (pro23his): a mouse model of autosomal dominant retinitis pigmentosa . Neuron . 1992;;9:815-830.

First Page Preview

First page PDF preview

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Watson JD, Crick FHC.  Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid . Nature . 1953;;171:737-738.
2 +
Culotta E.  New startups move in as gene therapy goes commercial . Science . 1993;;260:914-915.
3 +
Anderson WF.  Human gene therapy . Science . 1992;;256:808-813.
4 +
Miller AD.  Human gene therapy comes of age . Nature . 1992;;357:455-460.
5 +
Mulligan RC.  The basic science of gene therapy . Science . 1993;;260:926-932.
6 +
Lem J, Flannery JG, Li T, Applebury ML, Farber DB, Simon MI.  Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase beta subunit . Proc Natl Acad Sci U S A . 1992;;15:4422-4426.
7 +
Travis GH, Groshan KR, Lloyd M, Bok D.  Complete rescue of photoreceptor dysplasia and degeneration in transgenic retinal degeneration slow (rds) mice . Neuron . 1992;;9:113-119.
8 +
Kaiser-Kupfer MI, Caruso RC, Valle D.  Gyrate atrophy of the choroid and retina: long-term reduction of ornithine slows retinal degeneration . Arch Ophthalmol . 1991;;109:1539-1548.
9 +
Bok D.  Retinal transplantation and gene therapy: present realities and future possibilities . Invest Ophthalmol Vis Sci . 1993;;34:473-476.
10 +
Rosenfeld P, Cowley G, McGee T, Sandberg M, Berson E, Dryja T.  A null mutation in the rhodopsin gene causes rod photoreceptor dysfunction and autosomal recessive retinitis pigmentosa . Nature Genet . 1992;;1:209-213.
11 +
Musarella MA.  Gene mapping of ocular diseases . Surv Ophthalmol . 1992;;36:285-312.
12 +
Dryja TP, McGee TL, Hahn LB, et al.  Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa . N Engl J Med . 1990;;323:1302-1307.
13 +
Dryja TP, McGee TL, Reichel E, et al.  A point mutation of the rhodopsin gene in one form of retinitis pigmentosa . Nature . 1990;;343:364-366.
14 +
Sung C-H, Davenport CM, Hennesey JC, et al.  Rhodopsin mutations in autosomal dominant retinitis pigmentosa . Proc Natl Acad Sci U S A . 1991;;88:6481-6485.
15 +
Sheffield V, Fishman G, Beck J, Kimura A.  Identification of novel rhodopsin mutations associated with retinitis pigmentosa using GC-clamped denaturing gradient gel electrophoresis . Am J Hum Genet . 1991;;49:699-706.
16 +
McLaughlin ME, Sandberg MA, Berson EL, Dryja TP.  Recessive mutations in the gene encoding the β-subunit of rod phosphodiesterase in patients with retinitis pigmentosa . Nature Genet . 1993;;4:130-134.
17 +
Kajiwara K, Sandberg MA, Berson EL, Dryja TP.  A null mutation in the human peripherin/RDS gene in a family with autosomal dominant retinitis punctata albescens . Nature Genet . 1993;;3:208-212.
18 +
Nichols BE, Sheffield VC, Vandenburgh K, Drack AV, Kimura AE, Stone EM.  Butterfly-shaped pigment dystrophy of the fovea caused by a point mutation in codon 167 of the RDS gene . Nature Genet . 1993;;3:202-207.
19 +
Wells J, Wroblewski J, Keen J, et al.  Mutations in the human retinal degeneration slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy . Nature Genet . 1993;;3:213-218.
20 +
Berger W, Meindl A, van de Pol TJR, et al.  Isolation of a candidate gene for Norrie disease by positional cloning . Nature Genet . 1992;;1:199-203.
21 +
Chen Z-Y, Hendriks RW, Jobling MA, et al.  Isolation and characterization of a candidate gene for Norrie disease . Nature Genet . 1992;;1:204-208.
22 +
Nathans J, Davenport CM, Maumenee IH, et al.  Molecular genetics of human blue cone monochromacy . Science . 1989;;245:831-838.
23 +
Cremers FPM, van de Pol DJ, van Kerkhoff LP, Wieringa B, Ropers HH.  Cloning of a gene that is rearranged in patients with choroideremia . Nature . 1990;;347:674-677.
24 +
Merry DE, Janne PA, Landers JE, Lewis RA, Nussbaum RL.  Isolation of a candidate gene for choroideremia . Proc Natl Acad Sci U S A . 1992;;89:2135-2139.
25 +
Akli A, Caillaud C, Vigne E, et al.  Transfer of a foreign gene into the brain using adenovirus vectors . Nature Genet . 1993;;3:224-228.
26 +
Bajocchi G, Feldman SH, Crystal RG, Mastrangeli A.  Direct in vivo gene transfer to ependymal cells in the central nervous system using recombinant adenovirus vectors . Nature Genet . 1993;;3:229-234.
27 +
Davidson BL, Allen ED, Kozarsky KF, Wilson JM, Roessler BJ.  A model system for in vivo gene transfer into the central nervous system using an adenoviral vector . Nature Genet . 1993;;3:219-223.
28 +
Wagner E, Zatloukal K, Cotten M, et al.  Coupling of adenovirus to transferrin-polylysine/DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected genes . Proc Natl Acad Sci U S A . 1992;;89:6099-6103.
29 +
Zack DJ, Bennett J, Wang Y, et al.  Unusual topography of bovine rhodopsin promoter-lacZ fusion gene expression in transgenic mouse retinas . Neuron . 1991;;6:187-199.
30 +
Zack DJ. Analysis of retinal-specific gene expression in transgenic mice. In: Hargrave PA, ed. Methods in Neuroscience: Photoreceptor Cells. Orlando, Fla: Academic Press Inc. In press.
31 +
Lem J, Applebury ML, Falk JD, Flannery JG, Simon MI.  Tissue-specific and developmental regulation of rod opsin chimeric genes in transgenic mice . Neuron . 1991;;6:201-210.
32 +
Olsson JE, Gordon JW, Pawlyk BS, et al.  Transgenic mice with a rhodopsin mutation (pro23his): a mouse model of autosomal dominant retinitis pigmentosa . Neuron . 1992;;9:815-830.

Correspondence

Submit a Letter
CME Course for:


You need to register in order to view this quiz.


To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
To view and print your certificate and access a summary of your CME courses go to My CME.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
Submit a Comment

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

© 2012 American Medical Association. All Rights Reserved.
Powered bySilverchair Information Systems