|Year : 1968 | Volume
| Issue : 3 | Page : 109-115
Diabetic retinopathy - Concepts based on experimental data
PK Agrawal1, LP Agarwal1, HD Tandon2
1 Department of Ophthalmology, All-India Institute of Medical Sciences, New Delhi-16, India
2 Department of Pathology, All-India Institute of Medical Sciences, New Delhi-16, India
|Date of Web Publication||24-Dec-2007|
P K Agrawal
Department of Ophthalmology, All-India Institute of Medical Sciences, New Delhi-16
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Agrawal P K, Agarwal L P, Tandon H D. Diabetic retinopathy - Concepts based on experimental data. Indian J Ophthalmol 1968;16:109-15
|How to cite this URL:|
Agrawal P K, Agarwal L P, Tandon H D. Diabetic retinopathy - Concepts based on experimental data. Indian J Ophthalmol [serial online] 1968 [cited 2021 May 12];16:109-15. Available from: https://www.ijo.in/text.asp?1968/16/3/109/37531
Since the rediscovery of microaneurysms in diabetic retinopathy by Bellantyne and Loewenstein many hypothesis and theories have been advanced to explain the pathogenesis of micro-aneurysm formation.
The following is a list of such hypothesis:
A Systemic factors:
1. Hyperlipiemia IANNACCONE AND KORNERUP  ; ADLERSBERG, WANG, CH-I, RIFKIN, BERKMAN, PERKMAN, ROSS AND WEINSTEIN  .
2. Hyperlipoproteiniemia: KEIDING, MANN, ROOT, LAWRY AND MARBLE  ; BERKMAN, RIFKIN AND ROSS  .
3. Pituitary adrenal hyperactivity: BECKER  , BECKER, MAENGWYN-DAVIES, ROSEN, FRIEDENWALD AND WINTER  .
4. Formation of microthrombi: ASHTON  .
5. Hypercoagulability of blood: GORMSEN  .
6. Increased venous pressure (BALLANTYNE  .
B. Local factors:
1. Ectasia and weakening of the capillary wall: BALLANTYNE , .
2. Herniation of fat through the wall: POPE  .
3. Pathological alteration in the centrifugal nerves: WOLTER  .
4. Anoxia of the retina: WISE  .
5. Anoxic swelling of the retina and traction on the retinal vessels by mesodermal strands: (ASHTON  ).
6. Primary degeneration of the mural cells and the shunt mechanism: COGAN AND KUWABARA.  COGAN, TOUSSAINT AND KUWABARA  .
It can be seen from this list, the confused state of affairs as to the zetiogenesis of such microaneurysms. It is but natural that it should be so, because production of diabetic retinal lesions in any of the experimental animals has been hitherto unsatisfactory and unconvincing.- PATZ AND MAUMENEE,  HAUSLER, SIBAY, AND STACKOWSKA  HAUSLER, SIBAY AND CAMPBELL,  ENGERMANN, AND BLOODWORTH  .
The purpose of this communication is to report diabetic retinal lesions produced for the first time in albino rats, simulating human retinal microaneurysms. A possible morpho-physiopathological basis of microaneurysm formation is also being discussed.
Previous Work: We have reported on our studies on retinal capillaries, their development with special reference to the cellular structure and the retraction phenomenon of capillaries (AGRAWAL , ). In another communication we have reported on the reaction of retinal capillaries and their cellular elements to experimentally induced ischaemia (AGRAWAL  ).
It was concluded from these studies that in the capillary walls there are two types of cells, the endothelial and the mural cells both having derived from the same parent cell. [Figure - 1],[Figure - 2] The endothelial cells are large, oval with pale staining nuclei and situated along the long axis of the blood vessels. The mural cells have a rounded hyperchromatic nucleus and are enclosed within the basement membrane. Connecting the capillaries are intercapillary bands [Figure - 1], which may appear complete or incomplete, depending upon the degree of atrophy to which they are reduced after the process of retraction.
The mural cells are found at the junction of these capillary bands with the interconnected capillaries, as if guarding the entrance to these bands. [Figure - 1] A mural cell without an intercapillary band indicates the presence of a primitive capillary which has completely been absorbed.
The studies on experimental ischaemia indicate that the endothelial cells are first affected while the mural cells resist ischemia for a longer time, being enclosed in the basement membrane (Plate 3, a, b, c.)
| Methods and materials|| |
Albino rats were used as experimental animals and the retinal vessels were studied by trypsin (KUWABARA and COGAN, , ) or pepsin trpsin (ASHTON  ) digestion techniques.
Experimental diabetes was produced in two groups of animals (1) Alloxan diabetes (2) Diabetes by growth hormone and hydrocortisone (AGRAWAL AGARWAL and TANDON  ).
| OBSERVATIONS & COMMENTS|| |
Alloxan diabetic rats failed to reveal any retinal changes in the rats. It was only in animals with growth hormone and hydrocortisone that retinal changes were seen after six months of diabetes. Several interesting findings were seen. [Figure - 5],[Figure 6],[Figure 7],[Figure 8],[Figure 9],[Figure 10],[Figure 11],[Figure 12]. The first change was a loss of mural cells which was characteristic. [Figure - 5],[Figure 6]. They were preferentially lost from the capillaries giving rise to micro-aneurysms and from vessels over a considerable area in the surrounding neighbourhood. At quite a number of places a large number of ghost cells were present. [Figure 7],[Figure 8]. The microaneurysms came from vessels having normal or hyperplastic endothelial lining but they bordered on and were oriented towards areas in which the capillaries had lost all their cells. (Plate 4E, F). The endothelial population of vessels in which microaneurysms developed, increased while the capillaries which had lost all the cells did not show any aneurysmal dilatation. (Plate 4G, H). At the intercapillary bands when the mural cells were destroyed, there was an aggregation of endothelial cells. At places there was suggestion of the opening of the defunct bands. A multitude of microaneurysms were seen in all phases of development. (Plate 4 G. H).
The picture so described has not been seen in any of the experimentally produced diabetic retinal lesions. However most of the components have been described in this series of observations.
Thus we can see that while in experimental ischemia, the endothelial cells are first affected, in diabetes the cells to suffer first are the mural cells. The selective loss of mural cells in diabetes (COGAN and KUWABARA,  ) have led to great speculations about this selective action, for which no satisfactory explanation has yet been advanced.
The histochemical studies of diabetic retinal tissue indicate a depressed metabolic activity and production of a state of anoxia in the retinal tissues. This results in a primary involvement of the basement membrane of the retinal capillaries (BLOODWORTH  ). The mural cells cannot survive without the basement membrane in which they are enclosed and so we get a focal degeneration of mural cells in diabetic retinopathy. (AGRAWAL et al  ). As has already been shown the mural cells guard the intercapillary bands and once they degenerate, the control over the bands is lost. Under unregulated hydrodynamics due to the loss of mural cells these bands start opening and dilating. The type of aneurysm formation depends upon the type of band which has been opened up. An incomplete band will give rise to only a dilatation of the capillary while a complete one will give rise to neovascularization. (Explained in [Figure - 1]. Migration of endothelial cells in the opened up bands results in increased endothlial population in early micro-aneurysms. The degeneration and secondary deposits of hyaline results in obliteration of these aneurysms.
| Summary|| |
Experimental diabetic retinopathy was produced for the first time in albino rats by administration of growth hormone and hydrocortisone.
The histopathological changes so produced are described, and hypothecated (Agarwal's hypothesis) to explain the earlier degeneration of the basement membrance which encloses the mural cells. The subsequent changes, neovascularization, microaneurysm formation and aggregation of endothelial cells will result from the loss of the function of the valvular action of such mural cells which guard the entrance of intercapillary bands.
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[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]