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PubMed1987

Single-fiber electromyography is a sensitive indicator of axonal degeneration in diabetes.

Axonal degeneration with reinnervation was assessed in diabetic subjects with single-fiber electromyography (SF-EMG). SF-EMG was performed on 18 control subjects, 20 diabetic control subjects without clinical or electromyographic evidence of polyneuropathy, and 30 diabetic subjects with clinical and electromyographic features of polyneuropathy. In the diabetic controls and diabetic neuropathy subjects, fiber density and jitter were increased indicating axonal degeneration with reinnervation. These findings confirm that axonal degeneration is a principal pathologic mechanism in diabetic polyneuropathy and that axonal degeneration commonly occurs in asymptomatic diabetic subjects. SF-EMG is thus a sensitive method for assessing axonal degeneration in diabetic subjects.

Adult↗

PubMed2000

A Wallerian degeneration pattern in patients at risk for MS.

BACKGROUND: Demyelination alone may not explain the progressive disability that frequently develops in MS. An alternative explanation for irreversible disability assumes a contribution from axonal injury or loss. In theory, axonal injury may occur in the focal areas characterized by early inflammation, or can be more distant, as in Wallerian degeneration. However, Wallerian degeneration is thought of as a rare or a late finding in MS. METHODS: Studies showing a classic Wallerian degeneration pattern in the corticospinal tract were selected from a review of MR studies from patients enrolled in a longitudinal treatment trial. Entry was based on first occurrence of an isolated neurologic syndrome consistent with MS and a positive MRI. RESULTS: This report is based on five cases followed longitudinally who showed development of a classic T2-hyperintense lesion along the ipsilateral corticospinal tract, subsequent to an initial inciting event located in the white matter located in the superior aspect of the corona radiata. Lesions were evident as T2-hyperintensity persisting throughout the 12 to 18 months of observation. CONCLUSIONS: This series suggests that Wallerian degeneration, implying axonal injury, may occur as a sequela of acute demyelinating lesions in patients presenting with their first symptoms suggestive of MS. This can produce a component of the increasing burden of T2-hyperintense lesions temporally and spatially dissociated from inflammatory or demyelinating activity. Further studies are required to determine if Wallerian degeneration is an important factor contributing to disability progression in MS.

Adult↗

PubMed2006

Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy.

Axonal degeneration occurs in many neurodegenerative diseases and after traumatic injury and is a self-destructive program independent from programmed cell death. Previous studies demonstrated that overexpression of nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) or exogenous application of nicotinamide adenine dinucleotide (NAD) can protect axons of cultured dorsal root ganglion (DRG) neurons from degeneration caused by mechanical or neurotoxic injury. In mammalian cells, NAD can be synthesized from multiple precursors, including tryptophan, nicotinic acid, nicotinamide, and nicotinamide riboside (NmR), via multiple enzymatic steps. To determine whether other components of these NAD biosynthetic pathways are capable of delaying axonal degeneration, we overexpressed each of the enzymes involved in each pathway and/or exogenously administered their respective substrates in DRG cultures and assessed their capacity to protect axons after axotomy. Among the enzymes tested, Nmnat1 had the strongest protective effects, whereas nicotinamide phosphoribosyl transferase and nicotinic acid phosphoribosyl transferase showed moderate protective activity in the presence of their substrates. Strong axonal protection was also provided by Nmnat3, which is predominantly located in mitochondria, and an Nmnat1 mutant localized to the cytoplasm, indicating that the subcellular location of NAD production is not crucial for protective activity. In addition, we showed that exogenous application of the NAD precursors that are the substrates of these enzymes, including nicotinic acid mononucleotide, nicotinamide mononucleotide, and NmR, can also delay axonal degeneration. These results indicate that stimulation of NAD biosynthetic pathways via a variety of interventions may be useful in preventing or delaying axonal degeneration.

Animals↗

PubMed2006

Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death.

Alpha-synuclein (alpha-Syn) is enriched in nerve terminals. Two mutations in the alpha-Syn gene (Ala53--> Thr and Ala30--> Pro) occur in autosomal dominant familial Parkinson's disease. Mice overexpressing the human A53T mutant alpha-Syn develop a severe movement disorder, paralysis, and synucleinopathy, but the mechanisms are not understood. We examined whether transgenic mice expressing human wild-type or familial Parkinson's disease-linked A53T or A30P mutant alpha-syn develop neuronal degeneration and cell death. Mutant mice were examined at early- to mid-stage disease and at near end-stage disease. Age-matched nontransgenic littermates were controls. In A53T mice, neurons in brainstem and spinal cord exhibited large axonal swellings, somal chromatolytic changes, and nuclear condensation. Spheroid eosinophilic Lewy body-like inclusions were present in the cytoplasm of cortical neurons and spinal motor neurons. These inclusions contained human alpha-syn and nitrated synuclein. Motor neurons were depleted (approximately 75%) in A53T mice but were affected less in A30P mice. Axonal degeneration was present in many regions. Electron microscopy confirmed the cell and axonal degeneration and revealed cytoplasmic inclusions in dendrites and axons. Some inclusions were degenerating mitochondria and were positive for humanalpha-syn. Mitochondrial complex IV and V proteins were at control levels, but complex IV activity was reduced significantly in spinal cord. Subsets of neurons in neocortex, brainstem, and spinal cord ventral horn were positive for terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling, cleaved caspase-3, and p53. Mitochondria in neurons had terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive matrices and p53 at the outer membrane. Thus, A53T mutant mice develop intraneuronal inclusions, mitochondrial DNA damage and degeneration, and apoptotic-like death of neocortical, brainstem, and motor neurons.

Alanine↗

PubMed1992

Traumatic degeneration of transected myelinated fibers of the mouse sciatic nerve.

Traumatic degeneration of myelinated fibers was studied by electron microscopy over 5 days following transection of mouse sciatic nerve. Special attention was paid to the mechanism which separates the degenerating part, while preserving the viable part of the axon. Immediately after transection, the opened end of the proximal stump revealed extensive subcellular changes including the disorganization of neurofilaments, and disruption of mitochondria and axonal endoplasmic reticulum (SER). Subsequently, vesicles of round and tubular profiles filled up the whole area of the stump end, and proximal to it appeared a neurofilament-predominant area characterized by randomly oriented neurofilaments and normally appearing mitochondria and SER. Characteristic membranous demarcations occurred in early periods at the border between the vesicle accumulation and the neurofilament-predominant areas, and later also within these areas. The demarcation membranes formed both by invagination of the surface plasma membrane and, probably, by fusion of the large vesicles. These became prominent with time, dividing the axoplasm into compartments of varying sizes, which gradually underwent degeneration and were liberated from the parent axon. Occurrence of autophagic vacuoles was characteristic of the degenerating portions of the parent axon. Thus, by the function of demarcation membranes, the parent axon to be preserved could remain membrane-bound, while the degenerating parts were shed off.

Animals↗

PubMed2007

Inhibition of caspase-1/interleukin-1beta signaling prevents degeneration of retinal capillaries in diabetes and galactosemia.

The proinflammatory cytokine, interleukin (IL)-1beta, is known to induce vascular dysfunction and cell death. We investigated the role of IL-1beta and caspase-1 (the enzyme that produces it) in diabetes-induced degeneration of retinal capillaries. Caspase-1 activity is increased in retinas of diabetic and galactosemic mice and diabetic patients. First, we investigated the effect of agents known to inhibit caspase-1 (minocycline and tetracycline) on IL-1beta production and retinal capillary degeneration in diabetic and galactose-fed mice. Second, we examined the effect of genetic deletion of the IL-1beta receptor on diabetes-induced caspase activities and retinal capillary degeneration. Diabetic and galactose-fed mice were injected intraperitoneally with minocycline or tetracycline (5 mg/kg). At 2 months of diabetes, minocycline inhibited hyperglycemia-induced caspase-1 activity and IL-1beta production in the retina. Long-term administration of minocycline prevented retinal capillary degeneration in diabetic (6 months) and galactose-fed (13 months) mice. Tetracycline inhibited hyperglycemia-induced caspase-1 activity in vitro but not in vivo. Mice deficient in the IL-1beta receptor were protected from diabetes-induced caspase activation and retinal pathology at 7 months of diabetes. These results indicate that the caspase-1/IL-1beta signaling pathway plays an important role in diabetes-induced retinal pathology, and its inhibition might represent a new strategy to inhibit capillary degeneration in diabetic retinopathy.

Animals↗

PubMed2007

Contrasting roles for axonal degeneration in an autoimmune versus viral model of multiple sclerosis: When can axonal injury be beneficial?

Although demyelination is a cardinal feature in multiple sclerosis, axonal injury also occurs. We tested whether a delay in axonal degeneration could affect the disease severity in two models for multiple sclerosis: experimental autoimmune encephalomyelitis (EAE) and Theiler's murine encephalomyelitis virus (TMEV) infection. We compared wild-type C57BL/6 (B6) mice with C57BL/Wld(s) (Wld) mice, which carry a mutation that delays axonal degeneration. In EAE, both mouse strains were sensitized with myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide and showed a similar disease onset, MOG-specific lymphoproliferative responses, and inflammation during the acute stage of EAE. However, during the chronic stage, B6 mice continued to show paralysis with a greater extent of axonal damage, demyelination, and MOG-specific lymphoproliferative responses compared with Wld mice, which showed complete recovery. In TMEV infection, only Wld mice were paralyzed and had increased inflammation, virus antigen-positive cells, and TMEV-specific lymphoproliferative responses versus infected B6 mice. Because TMEV can use axons to disseminate in the brain, axonal degeneration in B6 mice might be a beneficial mechanism that limits the virus spread, whereas slow axonal degeneration in Wld mice could favor virus spread. Therefore, axonal degeneration plays contrasting roles (beneficial versus detrimental) depending on the initiator driving the disease.

Animals↗

PubMed2005

Electrophysiologic differentiation of homozygous and heterozygous Abyssinian-crossbred cats with late-onset hereditary retinal degeneration.

OBJECTIVE: To develop a method to electrophysiologically differentiate heterozygous-carrier Abyssinian-crossbred cats from homozygous-affected Abyssinian-crossbred cats before clinical onset of inherited rod-cone retinal degeneration. ANIMALS: 14 back-crossed Abyssinian-crossbred cats of unknown genotype (homozygous or heterozygous) for inherited rod-cone retinal degeneration, 24 age-matched mixed-breed control cats, 6 age-matched heterozygous Abyssinian-crossbred cats, and 6 homozygous Abyssinian cats. PROCEDURE: Electroretinography (ERG) of heterozygous and homozygous cats revealed differences, especially for scotopic recordings. Frequent ophthalmoscopy and ERG (2 to 5 times; at intervals of 3 to 6 months) of back-crossed cats were performed. Amplitudes and implicit times were analyzed by use of a graphic representation of results. Ratios for amplitudes of the b-waves to amplitudes of the a-waves (b-wave:a-wave) were compared. RESULTS: 8 back-crossed cats had decreased a-wave amplitudes, increased b-wave implicit times, and abnormal ERG waveforms. Values for the b-wave:a-wave for the highest scotopic light intensity were significantly higher for those same 8 cats. CONCLUSIONS AND CLINICAL RELEVANCE: The 8 back-crossed Abyssinian-crossbred cats with abnormal results developed fundus changes over time consistent with disease. A graphic representation of ERG results can be used to differentiate between genotypes prior to funduscopic changes. Values for the b-wave:a-wave ratio provide confirmation. These ERG analyses may be applied clinically in the diagnosis of retinal degenerations in various species. IMPACT FOR HUMAN MEDICINE: Cats with hereditary rod-cone degeneration may be a useful model for comparative studies in relation to retinitis pigmentosa in humans. Similar evaluations of ERG results could possibly be used for humans with suspected generalized retinal degeneration.

Animals↗

PubMed2000

Cerebellar degeneration in Old English Sheepdogs.

OBJECTIVE: To evaluate related and unrelated Old English Sheepdogs (OESD) by clinical examination, histologic evaluation, and pedigree analysis to determine whether cerebellar degeneration develops in this breed and whether there are genetic implications. DESIGN: Case study and pedigree analysis. ANIMALS: 24 clinically normal or affected OESD; brain tissue specimens from 25 unaffected or affected OESD. PROCEDURE: Twenty-four OESD that were chosen because of a family history of gait abnormalities were given physical and neurologic examinations to determine whether they had clinical signs of cerebellar degeneration. Tissue specimens from 25 brains of OESD were examined histologically. Nine OESD that were determined to have cerebellar degeneration histologically as well as 2 clinically affected littermates of the histologically confirmed affected OESD were included in the pedigree analysis. Standard statistical evaluation of pedigrees for hereditary conclusions was used. RESULTS: Twelve of the 24 OESD evaluated by neurologic examination had a progressive gait abnormality. Clinical signs of cerebellar degeneration typically started later in life in OESD, compared with description for other dog breeds, and progressed ore slowly. Results of pedigree analysis revealed that 11 of 49 dogs were affected in 9 litters, providing an affected-to-total ratio of 22.49%. CONCLUSIONS AND CLINICAL RELEVANCE: Results of our study indicate that a slowly progressing late-onset form of cerebellar degeneration develops in OESD, and the mode of inheritance is by an autosomal recessive gene.

Animals↗

PubMedDate not supplied

Extent of pyramidal tract wallerian degeneration in the brain stem on MRI and degree of motor impairment after supratentorial stroke.

The relationship between Wallerian degeneration in the brain stem and degree of motor impairment is discussed. Using MRI we studied 172 supratentorial stroke patients, whose motor impairment was graded according to Brunnstrom stage. Wallerian degeneration was represented by a T2 high-intensity area in the brain stem, and its cross-sectional extent was measured at the cerebral peduncle level. Wallerian degeneration was detected in 99 patients (57.6%). The area of T2 high intensity was significantly correlated with Brunnstrom stage. Multiple regression analysis showed that the upper extremity stage contributed most to the visualization of Wallerian degeneration. This is partly because the pyramidal tract participates in fine and precise movement. The extent of the area of Wallerian degeneration is found to be helpful in making a prognosis with respect to motor impairment in the upper extremity.

Adult↗

PubMed1980

A reliable method for demonstrating axonal degeneration shortly after axotomy.

A method has been elaborated by which degenerating axons can be selectively impregnated with silver. Based on reconsideration of the physicochemical mechanisms of the degeneration methods it takes advantage of physical developers over the chemical ones. The staining procedure is applied to frozen sections of brains fixed with formol. It consists of 6 steps: (1) pretreatment with alkaline hydroxylamine, (2) washing in acetic acid, (3) impregnation in silver nitrate in the presence of ferric ions, (4) washing in citric acid, (5) physical development, and (6) washing in acetic acid. By electron microscopy silver precipitates by this method are almost entirely restricted to the cytoplasm of dense, degenerating axons, sparing mitochondria and myelin sheaths. No special expertise is required to achieve reproducible results. Large numbers of sections treated simultaneously, and large sections, can be stained uniformly. Light microscopic criteria are described which help diagnose the source of possible failures. Low background staining allows dark field illumination and television image analysis to be applied. The method works at survival times of only 3 to 5 days after axotomy. Hence, degenerating axons and axon terminals can be stained in alternating sections from the same brain using this method and another being described separately, which, using different conditions, demonstrates degenerating axon terminals.

Animals↗

PubMed1980

A reliable and sensitive method to localize terminal degeneration and lysosomes in the central nervous system.

After reconsidering the physicochemical mechanisms involved in the so-called degeneration methods for the demonstration of axons and nerve terminals, the method of Eager was fundamentally modified in order to stabilize the staining process. This resulted in a simple and reliable method which stains degenerating terminals and lysosomes with a high degree of selectivity and sensitivity. Frozen sections 30 to 50 micrometers thick are prepared from material fixed with formaldehyde by cardiac perfusion. The staining procedure consists of 5 steps: 1) alkaline pretreatment (pH 13), 2) silver impregnation, 3) washing, 4) development at pH 5.0-5.5 monitored by an indicator, and 5) washing in acetic acid. Possible faults can be easily detected by their specific effects on the staining results. Primary submicroscopic silver precipitates are localized selectively in the osmiophilic parts of lysosomes and those degenerating presynaptic elements that are surrounded by glial processes. In degenerating axons, precipitates originating from mitochondria can usually be distinguished from terminal degeneration by their different size, shape, or characteristic arrangement. Nonspecific staining is restricted to glial fibrils, erythrocytes, and single cell nuclei. Dark field illumination can be applied routinely and television image analysis can be used for quantitative evaluation because of low background staining.

Animals↗

PubMed2000

Novel mechanism of massive photoreceptor degeneration caused by mutations in the trp gene of Drosophila.

The Drosophila trp gene encodes a light-activated Ca(2+) channel subunit, which is a prototypical member of a novel class of channel proteins. Previously identified trp mutants are all recessive, loss-of-function mutants characterized by a transient receptor potential and the total or near-total loss of functional TRP protein. Although retinal degeneration does occur in these mutants, it is relatively mild and slow in onset. We report herein a new mutant, Trp(P365), that does not display the transient receptor potential phenotype and is characterized by a substantial level of the TRP protein and rapid, semi-dominant degeneration of photoreceptors. We show that, in spite of its unusual phenotypes, Trp(P365) is a trp allele because a Trp(P365) transgene induces the mutant phenotype in a wild-type background, and a wild-type trp transgene in a Trp(P365) background suppresses the mutant phenotype. Moreover, amino acid alterations that could cause the Trp(P365) phenotype are found in the transmembrane segment region of the mutant channel protein. Whole-cell recordings clarified the mechanism underlying the retinal degeneration by showing that the TRP channels of Trp(P365) are constitutively active. Although several genes, when mutated, have been shown to cause retinal degeneration in Drosophila, the underlying mechanism has not been identified for any of them. The present studies provide evidence for a specific mechanism for massive degeneration of photoreceptors in Drosophila. Insofar as some human homologs of TRP are highly expressed in the brain, a similar mechanism could be a major contributor to degenerative disorders of the brain.

Amino Acid Sequence↗

PubMed2000

Impairment of rod cGMP-gated channel alpha-subunit expression leads to photoreceptor and bipolar cell degeneration.

PURPOSE: To determine whether alterations in rod cGMP-gated channel function mediate retinal degeneration, a transgenic approach in which the alpha subunit of the rod cGMP-gated channel is reduced by the expression of an antisense RNA was used. METHODS: A 890-bp fragment of the 5' mouse rod cGMP-gated channel cDNA was cloned in the antisense orientation under the control of the strong bacterial cytomegalovirus promoter. This antisense construct was used to generate transgenic mice in which the expression of the antisense transgene was measured by reverse transcription-polymerase chain reaction. Histologic, immunocytochemical, and TdT-dUTP terminal nick-end labeling (TUNEL) analyses were performed on control and transgenic retina sections to determine the effects of antisense expression on specific cell types. RESULTS: The antisense RNA was able to inhibit the translation of the rod channel protein in an in vitro assay. Three transgenic mouse lines expressing the antisense construct were obtained. Molecular analyses showed that the antisense is expressed in the eye of each transgenic mouse line, where it reduces rod cGMP-gated channel RNA expression. Histologic and immunocytochemical data showed that transgenic retinas have a reduced number of photoreceptors and bipolar cells. TUNEL staining confirmed that photoreceptor and bipolar cells degenerate along an apoptotic pathway. CONCLUSIONS: Impairment of rod cGMP-gated channel alpha subunit expression leads to photoreceptor and bipolar cell degeneration. These transgenic mice are the first model of retinal degeneration caused by an alteration in the expression of the rod cGMP-gated channel. This model system can be used to test therapies designed to slow or stalled retinal degenerations.

Animals↗

PubMed2001

[Age-related macular degeneration; therapeutic options].

The prevalence of age-related macular degeneration varies from 1% in patients aged 65 to 74 years, to 10% in patients aged 85 years and older. In the Netherlands, there is now a total of around 55,000 patients with age-related macular degeneration, and this figure is expected to rise to approximately 114,000 by 2025. Loss of central vision is caused by a degeneration of photoreceptors cells and pigment epithelium. Age-related macular degeneration is subdivided into a dry, atrophic form and an exudative form with neovascularisations. Many international studies have been published over the past ten years on potential new therapies for neovascular macular degeneration. For conventional laser treatment, it has been shown that visual loss in the long term is less marked in the treated group than in the observation group, despite the immediate destruction of the retina. Photodynamic therapy seems a promising new form of local therapy with few side-effects. For both therapies, however, the indication is limited to patients with the classic type of neovascularisation. Data on radiotherapy, submacular surgery and macular translocations are not sufficiently well-founded for firm conclusions to be drawn.

Age Factors↗

PubMed2002

[Wallerian degeneration demonstrated by MRI and functional outcome in patients suffering from supratentorial cerebrovascular disease].

An early diagnosis of the outcome of patients with cerebrovascular disease is important for selecting the optimal treatment strategy. The purpose of this study was to estimate the prognosis of Wallerian degeneration on MRI in stroke patients with hemiparesis. The subjects consisted of 87 stroke patients, 50 hemorrhagic patients and 37 ischemic patients, who were evaluated by MRI at 1 to 6,275 days after stroke onset. Among the 36 patients who were evaluated by consecutive MRI, 161 films were obtained and analyzed. Wallerian degeneration was diagnosed when a small prolonged T 2 lesion was seen in the corticospinal tract of the brainstem on at least two contiguous slices. The atrophic rate of the midbrain was calculated as: (the area of the unaffected side of the midbrain--the area of the affected side of the midbrain)/2 x (the area of the unaffected side of the midbrain). The patients' ability to perform the activities of daily living was scored by the Barthel index (BI). Wallerian degeneration in the ipsilateral brainstem was seen for two to three months in 32 cases (37%) and in 58 films (36%) and disappeared about 3 years after the onset of stroke. Wallerian degeneration correlated with the BI scores from 2 to 6 months after stroke (p < 0.05), although no relationship was observed at 7 months or later. From 2 to 6 months after stroke, the shrinkage of the midbrain on MRI correlated with the BI scores (p < 0.001), although no relationship was observed at 7 months or later. It was therefore both Wallerian degeneration and a shrunken midbrain observed on MRIs, evaluated from 2 to 6 months after stroke were thus suggested to indicate a poor outcome in such patients.

Adult↗

PubMed2002

Degeneration of myelinated efferent fibers induces spontaneous activity in uninjured C-fiber afferents.

We demonstrated recently that uninjured C-fiber nociceptors in the L4 spinal nerve develop spontaneous activity after transection of the L5 spinal nerve. We postulated that Wallerian degeneration leads to an alteration in the properties of the neighboring, uninjured afferents from adjacent spinal nerves. To explore the role of degeneration of myelinated versus unmyelinated fibers, we investigated the effects of an L5 ventral rhizotomy in rat. This lesion leads to degeneration predominantly in myelinated fibers. Mechanical paw-withdrawal thresholds were assessed with von Frey hairs, and teased-fiber techniques were used to record from single C-fiber afferents in the L4 spinal nerve. Behavioral and electrophysiological data were collected in a blinded manner. Seven days after surgery, a marked decrease in withdrawal thresholds was observed after the ventral rhizotomy but not after the sham operation. Single fiber recordings revealed low-frequency spontaneous activity in 25% of the C-fiber afferents 8-10 d after the lesion compared with only 11% after sham operation. Paw-withdrawal thresholds were inversely correlated with the incidence of spontaneous activity in high-threshold C-fiber afferents. In normal animals, low-frequency electrocutaneous stimulation at C-fiber, but not A-fiber, strength produced behavioral signs of secondary mechanical hyperalgesia on the paw. These results suggest that degeneration in myelinated efferent fibers is sufficient to induce spontaneous activity in C-fiber afferents and behavioral signs of mechanical hyperalgesia. Ectopic spontaneous activity from injured afferents was not required for the development of the neuropathic pain behavior. These results provide additional evidence for a role of Wallerian degeneration in neuropathic pain.

Action Potentials↗

PubMed2002

Retinal degeneration and RPE transplantation in Rpe65(-/-) mice.

PURPOSE: To determine whether transplanting normal retinal pigment epithelium (RPE) into the subretinal space influences photoreceptor function and degeneration in Rpe65(-/-) mice. METHODS: RPE cells were isolated from eyes of normal mice and transplanted to the subretinal space of one eye of Rpe65(-/-) mice. The other eye received a subretinal injection of saline or was not touched. Corneal electroretinograms (ERGs) from both eyes were monitored before and after surgery to follow progression of the degeneration. The width of the outer nuclear layer was measured in the area of transplantation and compared with a similar area in control retinas. RESULTS: Transplantation of RPE increased ERG amplitude maximally at 3.7 weeks after surgery. This rescue effect slowly diminished with time. Sham surgery had little effect on the ERG. The width of the outer nuclear layer in the area receiving RPE transplants was slightly greater than in control subjects. Evidence of the presence of RPE transplants in the subretinal space decreased with time after transplantation without signs of inflammation. CONCLUSIONS: Retinal degeneration in the Rpe65(-/-) mice is slowly progressive. Photoreceptor function can be transiently increased for several months and anatomic degeneration slightly reduced in Rpe65(-/-) mice by RPE cell transplantation. Loss of the rescue effect may be due to degeneration of the transplanted RPE.

Animals↗