Skip to main content
NCBI home page
The British Journal of Ophthalmology logoLink to The British Journal of Ophthalmology
. 2000 Mar;84(3):303–310. doi: 10.1136/bjo.84.3.303

Retinal ganglion cell death in experimental glaucoma

J Morgan 1, H Uchida 1, J Caprioli 1
PMCID: PMC1723413  PMID: 10684843

Abstract

AIMS—To determine whether parasol retinal ganglion cells (magnocellular pathway) are selectively lost in the primate model of glaucoma.
METHODS—Ocular hypertension was induced in one eye of six Macaca fascicularis monkeys for 6-14 weeks. The retinal ganglion cells in these eyes were labelled retrogradely with the tracer horseradish peroxidase (HRP) implanted into the optic nerve and subsequently examined in retinal whole mount preparations. The degree of retinal ganglion cell loss was estimated from Nissl stained tissue by comparison with the contralateral untreated control eye.
RESULTS—In the three glaucomatous retinas with the best labelling 1282 cells could be classified, of which 182 were parasol cells and 1100 were midget cells. Linear regression analysis did not demonstrate a significant reduction in the proportion of parasol to midget cells with increasing cell loss (regression slope 0.023, 95% CI −0.7 to 0.11). Compared with the control eye the cell soma of the remaining retinal ganglion cells in glaucomatous eyes were reduced in size by 20% for parasol cells (p=0.003) and by 16% for midget cells (p <0.001).
CONCLUSION—The results of this study do not support the hypothesis that selective loss of parasol retinal ganglion cells occurs in experimental glaucoma. In addition, the change in cell soma size distributions following ocular hypertension suggests that both parasol and midget retinal ganglion cells undergo shrinkage before cell death.



Full Text

The Full Text of this article is available as a PDF (191.1 KB).

Figure 1  .

Figure 1  

Open in a new tab

Sample grid used to count numbers of labelled and unlabelled cells. Spacing of sample points approximates in degrees the spacing of stimuli presented in automated perimetry with a Humphrey visual field analyser. The same areas have been numbered 1-52. Additional sample areas for more central locations are also shown (A-L). The visual field location corresponding to these retinal locations is given in degrees. The equivalent distance on the retinal surface is given in mm. On each axis, 0 corresponds to the centre of the fovea.

Figure 2  .

Figure 2  

Open in a new tab

Low power photomicrograph showing the pattern of retinal ganglion cell labelling in a macaque (animal 1487) with experimental glaucoma. The arrow indicates the focus of HRP labelling at the optic nerve head. Labelling was confined to the superotemporal retinal quadrant. Scale bar 1 mm.    

Figure 3  .

Figure 3  

Open in a new tab

Optic disc photograph showing thinning of the superior neuroretinal rim following ocular hypertension 4 days before HRP labelling (animal 1491). The arrow shows thinning of the neuroretinal rim and the quadrant of the optic nerve in which the HRP implantation was made. The contralateral normal disc is shown for comparison.

Figure 4  .

Figure 4  

Open in a new tab

Labelled cells in animal 1487. Eccentricity 7.35 mm. Typical parasol and midget cells are indicated (large and small arrows respectively). Scale bar 100 µm.       

Figure 5  .

Figure 5  

Open in a new tab

High power photomicrograph of retinal ganglion cells labelled with HRP in animal 1487. Eccentricity 2.4 mm. Large arrow indicates typical parasol cells. Small arrow indicates typical midget cells. Scale bar 50 µm.       

Figure 6  .

Figure 6  

Open in a new tab

Plot of the proportion of parasol cells to the sum of identified parasol and midget cells against cell loss. Samples were taken from 52 locations in three eyes. The unweighted regression line is continuous. The broken regression line is weighted for the number of typed cells (that is, P+M). The dotted line is weighted for the numbers of stained retinal ganglion cells used to estimate the degree of cell loss. Points corresponding to the animals providing these data (1487, 1491, and 1494) have been plotted with different markers.

Figure 7  .

Figure 7  

Open in a new tab

Histogram of cell soma size from for the normotensive eye. Sample areas were pooled with eccentricities in the range 3.5-3.8 mm. The broken line shows the soma sizes of cells that were insufficiently filled with HRP to be typed. Open circles = midget cells; solid squares = parasol cells.    

Figure 8  .

Figure 8  

Open in a new tab

Histogram of cell soma size from for eyes with ocular hypertension. Samples have been pooled in each case for the eccentricity ranges shown on the plot. The range of cell loss for the regions in which these cells were analysed is also shown. The broken line shows the soma sizes of cells that were insufficiently filled with HRP to be typed. Open circles = midget cells; solid squares = parasol cells.

Figure 9  .

Figure 9  

Open in a new tab

Comparison of mean cell soma sizes for parasol and midget cells in normal and glaucomatous retinas. Cells were pooled from eccentricities in the range 3.5-4.5 mm. The numbers on the bars indicate the number of cells to derive the mean soma area. Error bars show the standard deviation of the mean. Asterisks indicate that the difference in means is statistically significant (p <0.05).       

Figure 10  .

Figure 10  

Open in a new tab

(A) Mean cell soma size for parasol cells relative to the degree of cell loss relative to the contralateral eye. Error bars show the standard deviation of the mean. The numbers on the bars indicate the number of cells comprising the mean. Cells were pooled from eccentricities in the range 3.5-4.5 mm. NS = not statistically significant from control. (B) Mean cell soma size for parasol cells from the same range of eccentricities.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson D. R., Hendrickson A. Effect of intraocular pressure on rapid axoplasmic transport in monkey optic nerve. Invest Ophthalmol. 1974 Oct;13(10):771–783. [PubMed] [Google Scholar]
  2. Anderson R. S., O'Brien C. Psychophysical evidence for a selective loss of M ganglion cells in glaucoma. Vision Res. 1997 Apr;37(8):1079–1083. doi: 10.1016/s0042-6989(96)00260-x. [DOI] [PubMed] [Google Scholar]
  3. Bunt-Milam A. H., Dennis M. B., Jr, Bensinger R. E. Optic nerve head axonal transport in rabbits with hereditary glaucoma. Exp Eye Res. 1987 Apr;44(4):537–551. doi: 10.1016/s0014-4835(87)80162-8. [DOI] [PubMed] [Google Scholar]
  4. Burgoyne C. F., Quigley H. A., Thompson H. W., Vitale S., Varma R. Measurement of optic disc compliance by digitized image analysis in the normal monkey eye. Ophthalmology. 1995 Dec;102(12):1790–1799. doi: 10.1016/s0161-6420(95)30792-0. [DOI] [PubMed] [Google Scholar]
  5. Casson E. J., Johnson C. A., Shapiro L. R. Longitudinal comparison of temporal-modulation perimetry with white-on-white and blue-on-yellow perimetry in ocular hypertension and early glaucoma. J Opt Soc Am A Opt Image Sci Vis. 1993 Aug;10(8):1792–1806. doi: 10.1364/josaa.10.001792. [DOI] [PubMed] [Google Scholar]
  6. Chaturvedi N., Hedley-Whyte E. T., Dreyer E. B. Lateral geniculate nucleus in glaucoma. Am J Ophthalmol. 1993 Aug 15;116(2):182–188. doi: 10.1016/s0002-9394(14)71283-8. [DOI] [PubMed] [Google Scholar]
  7. Dacey D. M. Morphology of a small-field bistratified ganglion cell type in the macaque and human retina. Vis Neurosci. 1993 Nov-Dec;10(6):1081–1098. doi: 10.1017/s0952523800010191. [DOI] [PubMed] [Google Scholar]
  8. Dacey D. M., Petersen M. R. Dendritic field size and morphology of midget and parasol ganglion cells of the human retina. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9666–9670. doi: 10.1073/pnas.89.20.9666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dacey D. M., Petersen M. R. Dendritic field size and morphology of midget and parasol ganglion cells of the human retina. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9666–9670. doi: 10.1073/pnas.89.20.9666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dandona L., Hendrickson A., Quigley H. A. Selective effects of experimental glaucoma on axonal transport by retinal ganglion cells to the dorsal lateral geniculate nucleus. Invest Ophthalmol Vis Sci. 1991 Apr;32(5):1593–1599. [PubMed] [Google Scholar]
  11. Dreyer E. B. Selective cell death in glaucoma. Br J Ophthalmol. 1995 Jul;79(7):710–711. doi: 10.1136/bjo.79.7.710-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gaasterland D., Tanishima T., Kuwabara T. Axoplasmic flow during chronic experimental glaucoma. 1. Light and electron microscopic studies of the monkey optic nervehead during development of glaucomatous cupping. Invest Ophthalmol Vis Sci. 1978 Sep;17(9):838–846. [PubMed] [Google Scholar]
  13. Glovinsky Y., Quigley H. A., Pease M. E. Foveal ganglion cell loss is size dependent in experimental glaucoma. Invest Ophthalmol Vis Sci. 1993 Feb;34(2):395–400. [PubMed] [Google Scholar]
  14. Graham S. L., Drance S. M., Chauhan B. C., Swindale N. V., Hnik P., Mikelberg F. S., Douglas G. R. Comparison of psychophysical and electrophysiological testing in early glaucoma. Invest Ophthalmol Vis Sci. 1996 Dec;37(13):2651–2662. [PubMed] [Google Scholar]
  15. Hanker J. S., Yates P. E., Metz C. B., Rustioni A. A new specific, sensitive and non-carcinogenic reagent for the demonstration of horseradish peroxidase. Histochem J. 1977 Nov;9(6):789–792. doi: 10.1007/BF01003075. [DOI] [PubMed] [Google Scholar]
  16. Johnson C. A., Samuels S. J. Screening for glaucomatous visual field loss with frequency-doubling perimetry. Invest Ophthalmol Vis Sci. 1997 Feb;38(2):413–425. [PubMed] [Google Scholar]
  17. Marrocco R. T., McClurkin J. W., Young R. A. Spatial summation and conduction latency classification of cells of the lateral geniculate nucleus of macaques. J Neurosci. 1982 Sep;2(9):1275–1291. doi: 10.1523/JNEUROSCI.02-09-01275.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Matthews M. R., Cowan W. M., Powell T. P. Transneuronal cell degeneration in the lateral geniculate nucleus of the macaque monkey. J Anat. 1960 Apr;94(Pt 2):145–169. [PMC free article] [PubMed] [Google Scholar]
  19. Minckler D. S., Bunt A. H., Johanson G. W. Orthograde and retrograde axoplasmic transport during acute ocular hypertension in the monkey. Invest Ophthalmol Vis Sci. 1977 May;16(5):426–441. [PubMed] [Google Scholar]
  20. Moore S., Thanos S. Differential increases in rat retinal ganglion cell size with various methods of optic nerve lesion. Neurosci Lett. 1996 Mar 29;207(2):117–120. doi: 10.1016/0304-3940(96)12500-3. [DOI] [PubMed] [Google Scholar]
  21. Morgan J. E. Selective cell death in glaucoma: does it really occur? Br J Ophthalmol. 1994 Nov;78(11):875–880. doi: 10.1136/bjo.78.11.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Perry V. H., Cowey A. The ganglion cell and cone distributions in the monkey's retina: implications for central magnification factors. Vision Res. 1985;25(12):1795–1810. doi: 10.1016/0042-6989(85)90004-5. [DOI] [PubMed] [Google Scholar]
  23. Perry V. H., Linden R. Evidence for dendritic competition in the developing retina. Nature. 1982 Jun 24;297(5868):683–685. doi: 10.1038/297683a0. [DOI] [PubMed] [Google Scholar]
  24. Perry V. H., Oehler R., Cowey A. Retinal ganglion cells that project to the dorsal lateral geniculate nucleus in the macaque monkey. Neuroscience. 1984 Aug;12(4):1101–1123. doi: 10.1016/0306-4522(84)90006-x. [DOI] [PubMed] [Google Scholar]
  25. Potts A. M., Hodges D., Shelman C. B., Fritz K. J., Levy N. S., Mangnall Y. Morphology of the primate optic nerve. II. Total fiber size distribution and fiber density distribution. Invest Ophthalmol. 1972 Dec;11(12):989–1003. [PubMed] [Google Scholar]
  26. Quigley H. A., Dunkelberger G. R., Green W. R. Chronic human glaucoma causing selectively greater loss of large optic nerve fibers. Ophthalmology. 1988 Mar;95(3):357–363. doi: 10.1016/s0161-6420(88)33176-3. [DOI] [PubMed] [Google Scholar]
  27. Quigley H. A., Dunkelberger G. R., Green W. R. Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. Am J Ophthalmol. 1989 May 15;107(5):453–464. doi: 10.1016/0002-9394(89)90488-1. [DOI] [PubMed] [Google Scholar]
  28. Quigley H. A., Hohman R. M. Laser energy levels for trabecular meshwork damage in the primate eye. Invest Ophthalmol Vis Sci. 1983 Sep;24(9):1305–1307. [PubMed] [Google Scholar]
  29. Quigley H. A. Identification of glaucoma-related visual field abnormality with the screening protocol of frequency doubling technology. Am J Ophthalmol. 1998 Jun;125(6):819–829. doi: 10.1016/s0002-9394(98)00046-4. [DOI] [PubMed] [Google Scholar]
  30. Quigley H. A., Sanchez R. M., Dunkelberger G. R., L'Hernault N. L., Baginski T. A. Chronic glaucoma selectively damages large optic nerve fibers. Invest Ophthalmol Vis Sci. 1987 Jun;28(6):913–920. [PubMed] [Google Scholar]
  31. Quigley H. A. Selectivity in glaucoma injury. Arch Ophthalmol. 1998 Mar;116(3):396–398. [PubMed] [Google Scholar]
  32. Quigley H. A. Selectivity in glaucoma injury. Arch Ophthalmol. 1998 Mar;116(3):396–398. [PubMed] [Google Scholar]
  33. Reese B. E., Guillery R. W. Distribution of axons according to diameter in the monkey's optic tract. J Comp Neurol. 1987 Jun 15;260(3):453–460. doi: 10.1002/cne.902600310. [DOI] [PubMed] [Google Scholar]
  34. Sample P. A., Bosworth C. F., Weinreb R. N. Short-wavelength automated perimetry and motion automated perimetry in patients with glaucoma. Arch Ophthalmol. 1997 Sep;115(9):1129–1133. doi: 10.1001/archopht.1997.01100160299006. [DOI] [PubMed] [Google Scholar]
  35. Silveira L. C., Perry V. H. The topography of magnocellular projecting ganglion cells (M-ganglion cells) in the primate retina. Neuroscience. 1991;40(1):217–237. doi: 10.1016/0306-4522(91)90186-r. [DOI] [PubMed] [Google Scholar]
  36. Vickers J. C., Schumer R. A., Podos S. M., Wang R. F., Riederer B. M., Morrison J. H. Differential vulnerability of neurochemically identified subpopulations of retinal neurons in a monkey model of glaucoma. Brain Res. 1995 May 22;680(1-2):23–35. doi: 10.1016/0006-8993(95)00211-8. [DOI] [PubMed] [Google Scholar]
  37. Wall M., Jennisch C. S., Munden P. M. Motion perimetry identifies nerve fiber bundlelike defects in ocular hypertension. Arch Ophthalmol. 1997 Jan;115(1):26–33. doi: 10.1001/archopht.1997.01100150028003. [DOI] [PubMed] [Google Scholar]
  38. Weber A. J., Kaufman P. L., Hubbard W. C. Morphology of single ganglion cells in the glaucomatous primate retina. Invest Ophthalmol Vis Sci. 1998 Nov;39(12):2304–2320. [PubMed] [Google Scholar]
  39. Wingate R. J. Retinal ganglion cell dendritic development and its control. Filling the gaps. Mol Neurobiol. 1996 Apr;12(2):133–144. doi: 10.1007/BF02740650. [DOI] [PubMed] [Google Scholar]

Articles from The British Journal of Ophthalmology are provided here courtesy of BMJ Publishing Group

RESOURCES