The structural and neurochemical development of the fetal guinea pig retina and optic nerve in experimental growth retardation

Abstract

In this study we have examined structural and neurochemical aspects of retinal and optic nerve development in experimentally growth-retarded fetal guinea pigs following maternal unilateral artery ligation. Eye weight (n = 4) and total retinal area (n = 6) at 62 days gestation (term approximately 66 days) were both relatively spared when expressed as a percentage of body weight but in absolute terms were significantly reduced by 18% (P less than 0.001) and 13% (P less than 0.05) respectively when compared with age-matched controls. The numerical density of neurons in the ganglion cell layer was significantly higher at both 52 days (n = 4) and 62 days (n = 4) in growth-retarded fetuses compared with controls. However, there was no difference between the groups in the total number of neurons in this retinal layer at either age, since retinal areas are reduced in growth retardation. The area of neuronal somata in the ganglion and inner nuclear layers was significantly reduced in growth-retarded fetuses compared with controls. There was a concomitant reduction in the width of the cellular layers in the retina and also in the plexiform (synaptic) and photoreceptor layers. The growth of the outer segments of the photoreceptor layer was particularly affected in peripheral retina. The higher packing density of cells and the reduced growth of the plexiform layers suggests a reduction in the growth of the neuropile in growth-retarded fetuses compared with controls. The radial bundling of ganglion cell axons coursing across the retina to enter the optic nerve head was poorly defined in growth retardation. In addition myelination was delayed in the optic nerve with the numerical density of myelinated axons being significantly reduced (P less than 0.005) in growth-retarded fetuses compared with controls. There was a significant reduction (P less than 0.01) in the number of amacrine cells in the inner plexiform layer expressing Substance P-like immunoreactivity in growth-retarded fetuses compared with controls. Glutamate-like immunoreactivity was most intense in the five laminae of the inner plexiform layer and in the outer plexiform layer and less pronounced in photoreceptors, ganglion cells and their axons. There was no qualitative difference in glutamate immunoreactivity between control and growth-retarded fetuses in any of these structures. Thus we have shown that intrauterine growth retardation has specific effects on the development of the fetal guinea pig retina, reducing the growth of several types of neurons and their processes and affecting the expression of the neuropeptide substance-P in amacrine cells.

Chronic placental insufficiency in the fetal guinea pig affects neurochemical and neuroglial development but not neuronal numbers in the brainstem: A new method for combined stereology and immunohistochemistry

“…Brain weight was also reduced in experimental animals but was relatively spared when compared to controls as evidenced by the increased brain:body and brain:liver ratios. These results are comparable to previous findings (Lafeber et al, 1984;Nitsos and Rees, 1990;Rees and Bainbridge, 1992), however a result not reported previously was a significant reduction in the brainstem weight in GR compared to control fetuses. It is known from previous work that these GR fetuses are chronically hypoxic, malnourished (Jones and Parer, 1983), and have an altered endocrine balance (Jones et al, 1987).…”

“…The results show that there was no significant difference in the number of motor neurons in the hypoglossal nucleus of GR compared to control fetuses, a finding which confirms previous studies on the trochlear nucleus of GR sheep ) and on retinal ganglion cells in GR guinea pigs (Rees and Bainbridge, 1992). As the counts are made at the end of the period of cell death, it is possible that a reduction in neurogenesis has been compensated for by a reduction in programmed cell death.…”

“…several years of experience using this model in our laboratory has shown that they do not differ from unoperated animals in any of the parameters that we have measured so far (Bisignano and Rees, 1988;Nitsos and Rees, 1990;Rees and Bainbridge, 1992). Thirteen (26.5%) of the 49 fetuses were classified as GR (see below), with 11 (84.6%) obtained from the ligated horn and two (15.4%) from the unligated horn.…”

“…This conclusion is supported by the observation that GFAP staining was similar in the control and GR fetuses indicating that astroglial numbers have not been affected. In previous studies of GR sheep and guinea pigs at term, it has been shown that the growth of neuronal processes has been significantly reduced in visual cortical neurons (Bisignano and Rees, 1988), cerebellar Purkinje cells , and retinal ganglion cells (Rees and Bainbridge, 1992). As this does not appear to be the case for the hypoglossal nucleus it is possible that the nucleus is privileged in terms of supply of oxygen and nutrients and therefore not compromised in the growth of processes.…”

Abnormal Retinal Optic Nerve Morphology in Young Adults after Intrauterine Growth Restriction

“…The observed reduction in axonal area in subjects with IUGR may reflect either reduced axonal growth with a reduction of axonal volume or a decrease in the number of axons, i.e., in the number of neurons. Experimentally growth restricted fetal guinea pigs had signs of delayed myelination with a reduced density of myelinated axons in the optic nerve when examined shortly before term (17). In addition, these changes were accompanied by a reduced width of cellular layers in the retina and an unaffected number of neurons in the ganglion cell layer (higher density but reduced retinal area), suggesting a reduction in the growth of the neuropile.…”