PROGRAMMED CELL-DEATH OF RETINAL GANGLION-CELLS DURING EXPERIMENTAL GLAUCOMA

被引:405
作者
GARCIAVALENZUELA, E [1 ]
SHAREEF, S [1 ]
WALSH, J [1 ]
SHARMA, SC [1 ]
机构
[1] NEW YORK MED COLL, DEPT OPHTHALMOL, VALHALLA, NY 10595 USA
关键词
APOPTOSIS; GLAUCOMA; RETINA; CYCLOHEXIMIDE; TERMINAL-DEOXYNUCLEOTIDYL-TRANSFERASE; INTRAOCULAR-PRESSURE;
D O I
10.1016/S0014-4835(95)80056-5
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
The death of retinal ganglion cells during glaucoma is thought to result from damage to their axons as they exit the eye through the lamina cribrosa. In this study, intraocular pressure in the rat was increased to twice the normal averge by cauterizing two limbal-derived veins. To investigate whether retinal ganglion cells in the glaucomatous eye follow an apoptotic type of death, DNA breaks in nuclei were labeled in situ, using a method that specifically incorporates biotinylated deoxynucleotides by exogenous terminal deoxynucleotidyl transferase to the 3'-OH ends of DNA. The active nature of the death mechanism was demonstrated by the reduction in numbers of biotin-labeled nuclei after administration of the protein synthesis inhibitor, cycloheximide. Our results suggest that retinal ganglion cells of the adult rat die through apoptosis when the intraocular pressure is markedly increased. This raises new possibilities in the treatment of glaucomatous damage to the retina, by the potential interruptibility of a program for neuronal death. (C) 1995 Academic Press Limited
引用
收藏
页码:33 / 44
页数:12
相关论文
共 35 条
[1]  
ABRAMS L, 1994, INVEST OPHTH VIS SCI, V35, P1857
[2]   BIOSTATISTICAL ANALYSIS OF THE COLLABORATIVE GLAUCOMA STUDY .1. SUMMARY REPORT OF THE RISK-FACTORS FOR GLAUCOMATOUS VISUAL-FIELD DEFECTS [J].
ARMALY, MF ;
KRUEGER, DE ;
MAUNDER, L ;
BECKER, B ;
HETERINGTON, J ;
KOLKER, AE ;
LEVENE, RZ ;
MAUMENEE, AE ;
POLLACK, IP ;
SHAFFER, RN .
ARCHIVES OF OPHTHALMOLOGY, 1980, 98 (12) :2163-2171
[3]   AXOTOMY RESULTS IN DELAYED DEATH AND APOPTOSIS OF RETINAL GANGLION-CELLS IN ADULT-RATS [J].
BERKELAAR, M ;
CLARKE, DB ;
WANG, YC ;
BRAY, GM ;
AGUAYO, AJ .
JOURNAL OF NEUROSCIENCE, 1994, 14 (07) :4368-4374
[4]  
BRAY GM, 1991, ANN NY ACAD SCI, V633, P214, DOI DOI 10.1111/J.1749-6632.1991.TB15613.X)
[5]  
CAMPBELL DG, 1980, PERSPECT OPHTHALMOL, V4, P123
[6]  
DANDONA L, 1991, INVEST OPHTH VIS SCI, V32, P1593
[7]   FEATURES OF APOPTOTIC CELLS MEASURED BY FLOW-CYTOMETRY [J].
DARZYNKIEWICZ, Z ;
BRUNO, S ;
DELBINO, G ;
GORCZYCA, W ;
HOTZ, MA ;
LASSOTA, P ;
TRAGANOS, F .
CYTOMETRY, 1992, 13 (08) :795-808
[8]   MUSCLE-DERIVED FACTORS THAT SUPPORT SURVIVAL AND PROMOTE FIBER OUTGROWTH FROM EMBRYONIC CHICK SPINAL MOTOR NEURONS IN CULTURE [J].
DOHRMANN, U ;
EDGAR, D ;
SENDTNER, M ;
THOENEN, H .
DEVELOPMENTAL BIOLOGY, 1986, 118 (01) :209-221
[9]   THE DEATH PROGRAM IN CULTURED SYMPATHETIC NEURONS CAN BE SUPPRESSED AT THE POSTTRANSLATIONAL LEVEL BY NERVE GROWTH-FACTOR, CYCLIC-AMP, AND DEPOLARIZATION [J].
EDWARDS, SN ;
BUCKMASTER, AE ;
TOLKOVSKY, AM .
JOURNAL OF NEUROCHEMISTRY, 1991, 57 (06) :2140-2143
[10]   CELL-DEATH AND THE CREATION OF REGIONAL DIFFERENCES IN NEURONAL NUMBERS [J].
FINLAY, BL .
JOURNAL OF NEUROBIOLOGY, 1992, 23 (09) :1159-1171