Peter Naeser

Effects of adrenalectomy on the obese-hyperglycemic syndrome in mice (gene symbolob)

SummaryMice with the inherited obese-hyperglycemic syndrome (gene symbolob) and their lean litter mates were adrenalectomized and then studied for up to 30–36 weeks with regard to their body weights and the serum glucose and immunoreactive insulin level. Sham operated obese and lean mice were used as controls.-Adrenalectomy did not prevent the excessive weight gain of the obese mice. However, during the first three weeks after adrenalectomy the mean weight increase was some-what smaller than in the sham operated controls. The increase in the body weights of the lean animals was, however, not affected. The most prominent finding after adrenalectomy was a decrease of the serum levels of glucose and insulin in both obese and lean animals.-The results indicate that in the obese mice adrenalectomy decreases the pronounced insulin resistance. It is also suggested that insulin resistance may be dissociated from the development of obesity in these animals.

TUMOURS OF THE ORBIT DIAGNOSED BY FINE NEEDLE BIOPSY

Fine needle aspiration biopsies were used for the diagnosis of orbital tumours. Examples of benign and malignant primary and metastatic orbital neoplasms, as well as inflammatory lesions diagnosed in this way are described. The method has proved of great value. This was specially true for processes located posteriorly in the orbit. The necessity for close cooperation between the ophthalmological and clinical cytological departments is emphasized.

Insulin Receptors in Human Ocular Tissues Immunohistochemical demonstration in normal and diabetic eyes

The alpha- and beta-subunits of the insulin receptor have been localised in human eyes by immunohistochemistry. In the normal eye staining for both receptor subunits was distinct at the same sites of the anterior part of the eye, i.e. cornea, smooth muscle and epithelium of the ciliary body and the lens capsule. In the retina, the receptor was clearly demonstrated in the nerve fibre layer, the ganglion cells and Müller cells, the outer nuclear layer, inner segments of rods and cones, the outer limiting membrane and in the pigment epithelium. In eyes with diabetic retinopathy, the receptor did not stain in the inner segments of the rods and cones and the staining of the other layers was weak. Endothelial cells stained positively in normal and diabetic eyes, but pericytes of normal and new vessels did not stain. The receptor staining did not change in cornea, iris, ciliary body and lens. All together, the study shows that alpha- and beta-subunits of the insulin receptor are present in the retina, and that the staining reaction for the receptor is reduced in diabetes. To what extent these findings are of importance for the development of diabetic retinopathy, remains to be clarified.

Function of the adrenal cortex in obese-hyperglycemic mice (gene symbol ob).

SummaryThe adrenal function of the obese-hyperglycemic mouse has been analysed by measurements of serum corticosteroid levels at different ages and after various types of stimulation. In addition, the corticosteroid binding capacity (CBC) of the serum was evaluated in these animals. The results showed that in all ages investigated the obese hyperglycemic animals had significantly elevated values of serum corticosteroids compared with their lean controls. This difference did not vary with age. Both administration of ACTH and stressful handling further increased the corticosteroid values of the obese animals. In addition, the CBC was significantly elevated in these animals at the ages of 6 and 16 months. Since the serum corticosteroid levels, in contrast to other manifestations of the obese-hyperglycemic syndrome, did not vary with age, it is suggested that the hyperadrenocorticism observed in these animals is not of primary aetiological significance for the development of the syndrome. This does not preclude the possibility that a prolonged elevation of serum corticosteroid levels contributes to the syndrome.

Photoreceptor allografts in a feline model of retinal degeneration.

Abstract · Background: Photoreceptor transplants provide a potential means to restore function in a degenerate retina and/or rescue degenerating host photoreceptors by trophic influences. We have examined photoreceptor allografts in the Abyssinian cat model of hereditary photoreceptor degeneration to determine the viability and influence of such transplants on the host retina. · Methods: Small pieces of 3- to 5-day-old normal kitten retina containing undifferentiated photoreceptors were injected into the subretinal space of adult Abyssinian cats at an early stage of retinal degeneration using standard vitreo-retinal surgical techniques. The retinas were examined by ophthalmoscopy and fundus photography, then by light and electron microscopy at different times after surgery. · Results: Such allografts survive for at least 6 months after surgery. The photoreceptors develop outer segments, invariably in rosettes. The transplants gradually integrate with the host retina but detach the host photoreceptor layer from the retinal pigment epithelium (RPE), which tends to reduce the number of host photoreceptors over the transplant. There is no slowing of the photoreceptor degeneration in neighboring non-detached retina. Inflammation or rejection was not detected. · Conclusion: Undifferentiated, neonatal photoreceptor allografts survive and develop outer segments in the subretinal space of the Abyssinian mutant feline retina. The allografts gradually integrate with the host neural retina without inducing rejection. In the vicinity of the transplant there is increased loss of host photoreceptors, considered to be due to their detachment from the RPE layer. There is no evidence of any rescue of host photoreceptors elsewhere in this mutant retina.

Retinoblastoma in Sweden 1958--1971. A clinical and histopathological study.

This study includes all cases of retinoblastoma reported in Sweden between 1958 and 1971. The incidence of the disease was 1 per 18 000 live births. Only in six cases was there a familial history and five of these cases were bilateral. The tumour was bilateral in 37.5 % of all cases. All cases with unilateral tumour had been treated with enucleation. In the bilateral cases one eye had also been enucleated and the other eye treated by local irradiation therapy. Tumour invasion into choroid was found in 29% and into the optic nerve in 11% of the cases. The mortality was only 4.5%.

Effects of long-term chloroquine exposure on the phospholipid metabolism in retina and pigment epithelium of the mouse

Abstract The influence of 6 months treatment of normal mice with chloroquine on neuroretina and retinal pigment epithelium has been investigated biochemically and morphologically. All classes of neuroretinal phospholipids, except lysophosphatidylcholine, showed increased 14C‐glucose incorporation after chloroquine treatment. No metabolic changes were observed in the pigment epithelium after the chloroquine treatment. Morphological signs of phospholipidosis were only evident in the ganglion cells of the neuroretina. It is concluded that long‐term treatment with chloroquine does not affect pigment epithelium phospholipid metabolism but leads to morphological and biochemical signs of phospholipidosis in the neuroretina.

DNA replication in transplanted and endogenous pancreatic islets of obese-hyperglycemic mice at different stages of the syndrome

It was the aim of the present study to examine, at different stages of the obese-hyperglycemic syndrome, rates of islet-cell DNA replication in endogenous pancreatic and grafted islets of such mice. For this purpose obese-hyperglycemic mice were given an islet transplant prepared from lean mice under the kidney capsule. Two weeks later the animals were given an IP injection of 3H-thymidine one hour before being killed. Autoradiography of pancreas and kidney sections indicated the highest labeling index (LI) for the endogenous islet cells in the youngest obese mice (6 weeks old), which was more than fivefold higher than that of lean, normoglycemic controls. The LI, however, decreased extensively with age. The transplanted islets had LI, which were higher and constant during the most intense period of the syndrome, but again there was a decrease in the oldest mice. By isolating and transplanting islets of the oldest obese mice (greater than 12 months) into younger obese mice, it was possible to revive the high cell replicatory activity of the ob/ob islets. Starvation for three days was found to markedly decrease the rate of islet cell DNA replication. Adrenalectomy of obese-hyperglycemic mice resulted in a decrease of the serum glucose and insulin concentrations; concomitantly, there was a decrease of LI of both transplanted and endogenous islets. Thus, it seems as if the attenuation of the hyperglycemia is most probably responsible for the decline of the islet cell replication with increasing age in obese-hyperglycemic mice.

Changes in MR of Malignant Melanomas Induced by Glucose and Fructose: A clinical and experimental investigation

MR imaging has been performed on malignant melanomas in vitro and in vivo. Changes of the water content in an enucleated malignant melanoma in vitro were followed by significant changes of the T1 and T2 values. In mice with implanted subcutaneous melanoma similar changes could be obtained after injection of glucose and fructose intraperitoneally. Malignant melanoma of the eye could be influenced in the same way in 10 consecutive patients after oral intake of glucose and fructose. The present study shows that the MR images may be significantly changed after a few hours by altered metabolism induced by glucose and fructose. It is anticipated that this is due to changes within the tumor leading to different water distribution. The finding may be of importance as a further help for diagnosing malignant melanoma of the eye.

Effects of pancreatic islet implantation on the morphology of retinal capillaries in alloxan diabetic mice.

Intrasplenic implantation of syngeneic islets normalized the hyperglycaemia of alloxan‐diabetic mice irrespective of whether the implantation was performed 2 weeks or 4 months after the induction of diabetes. Islet implantation soon after the onset of diabetes prevented the development of retinal capillary disease as evidenced by a normal ratio between endothelial cells and pericytes. The increase of the cell count ratio (endothelial cells/pericytes) induced by long‐term diabetes could not, however, be restored by islet implantation. The present results further underline the importance of optimal treatment for prevention of diabetic retinopathy.